Radio Biophysics Level 3

Reactor Concepts Manual Biological Effects of Radiation
Biological
Effects of
Radiation
Whether the source of radiation is

natural or man-made, whether it is a
small dose of radiation or a large dose,
there will be some biological effects.
This chapter summarizes the short and
long term consequences which may
result from exposure to radiation.
USNRC Technical Training Center 9-1 0603

Radiation Causes Ionizations of:
ATOMS
which may affect
MOLECULES
which may affect
CELLS
which may affect
TISSUES
which may affect
ORGANS
which may affect
THE WHOLE BODY
Although we tend to think of biological effects in terms of the effect of radiation on living cells, in
actuality, ionizing radiation, by definition, interacts only with atoms by a process called ionization.
Thus, all biological damage effects begin with the consequence of radiation interactions with the atoms
forming the cells. As a result, radiation effects on humans proceed from the lowest to the highest levels
as noted in the above list.

CELLULAR DAMAGE
Even though all subsequent biological effects can be traced back to the interaction of radiation with
atoms, there are two mechanisms by which radiation ultimately affects cells. These two mechanisms
are commonly called direct and indirect effects.

Direct Effect
Damage
To DNA
From
Ionization
If radiation interacts with the atoms of the DNA molecule, or some other cellular component critical to
the survival of the cell, it is referred to as a direct effect. Such an interaction may affect the ability of
the cell to reproduce and, thus, survive. If enough atoms are affected such that the chromosomes do not
replicate properly, or if there is significant alteration in the information carried by the DNA molecule,
then the cell may be destroyed by “direct” interference with its life-sustaining system.

Indirect Effect
Radiolytic Decomposition of Water in a Cell
If a cell is exposed to radiation, the probability of the radiation interacting with the DNA molecule is
very small since these critical components make up such a small part of the cell. However, each cell,
just as is the case for the human body, is mostly water. Therefore, there is a much higher probability of
radiation interacting with the water that makes up most of the cell’s volume.
When radiation interacts with water, it may break the bonds that hold the water molecule together,
producing fragments such as hydrogen (H) and hydroxyls (OH). These fragments may recombine or may
interact with other fragments or ions to form compounds, such as water, which would not harm the cell.
However, they could combine to form toxic substances, such as hydrogen peroxide (H2O2), which can
contribute to the destruction of the cell.

Cellular Sensitivity to Radiation

(from most sensitive to least sensitive)
Lymphocytes and Blood Forming Cells
Reproductive and Gastrointestinal (GI) Cells
Nerve and Muscle Cells
Not all living cells are equally sensitive to radiation. Those cells which are actively reproducing are
more sensitive than those which are not. This is because dividing cells require correct DNA information
in order for the cell’s offspring to survive. A direct interaction of radiation with an active cell could
result in the death or mutation of the cell, whereas a direct interaction with the DNA of a dormant cell
would have less of an effect.
As a result, living cells can be classified according to their rate of reproduction, which also indicates
their relative sensitivity to radiation. This means that different cell systems have different sensitivities.
Lymphocytes (white blood cells) and cells which produce blood are constantly regenerating, and are,
therefore, the most sensitive. Reproductive and gastrointestinal cells are not regenerating as quickly and
are less sensitive. The nerve and muscle cells are the slowest to regenerate and are the least sensitive
cells.

NORMAL REPAIR OF DAMAGE CELL DIES FROM DAMAGE
NO REPAIR OR NON-IDENTICAL
DAUGHTER CELLS DIE
REPAIR BEFORE REPRODUCTION
Cells, like the human body, have a tremendous ability to repair damage. As a result, not all radiation
effects are irreversible. In many instances, the cells are able to completely repair any damage and
function normally.
If the damage is severe enough, the affected cell dies. In some instances, the cell is damaged but is still
able to reproduce. The daughter cells, however, may be lacking in some critical life-sustaining
component, and they die.
The other possible result of radiation exposure is that the cell is affected in such a way that it does not
die but is simply mutated. The mutated cell reproduces and thus perpetuates the mutation. This could
be the beginning of a malignant tumor.

Organ Sensitivity
(from most sensitive to least sensitive)
Blood Forming Organs
Reproductive and Gastrointestinal Tract Organs
Skin
Muscle and Brain
The sensitivity of the various organs of the human body correlate with the relative sensitivity of the cells
from which they are composed. For example, since the blood forming cells were one of the most
sensitive cells due to their rapid regeneration rate, the blood forming organs are one of the most sensitive
organs to radiation. Muscle and nerve cells were relatively insensitive to radiation, and therefore, so are
the muscles and the brain.

Sensitivity
Rate of Reproduction
Oxygen Supply
The rate of reproduction of the cells forming an organ system is not the only criterion determining
overall sensitivity. The relative importance of the organ system to the well being of the body is also
important.
One example of a very sensitive cell system is a malignant tumor. The outer layer of cells reproduces
rapidly, and also has a good supply of blood and oxygen. Cells are most sensitive when they are
reproducing, and the presence of oxygen increases sensitivity to radiation. Anoxic cells (cells with
insufficient oxygen) tend to be inactive, such as the cells located in the interior of a tumor.
As the tumor is exposed to radiation, the outer layer of rapidly dividing cells is destroyed, causing it to
“shrink” in size. If the tumor is given a massive dose to destroy it completely, the patient might die as
well. Instead, the tumor is given a small dose each day, which gives the healthy tissue a chance to
recover from any damage while gradually shrinking the highly sensitive tumor.
Another cell system that is composed of rapidly dividing cells with a good blood supply and lots of
oxygen is the developing embryo. Therefore, the sensitivity of the developing embryo to radiation
exposure is similar to that of the tumor, however, the consequences are dramatically different.

Whole Body Sensitivity Factors
Total Dose
Type of Cell
Type of Radiation
Age of Individual
Stage of Cell Division
Part of Body Exposed
General State of Health
Tissue Volume Exposed
Time Interval over which Dose is Received
Whole body sensitivity depends upon the most sensitive organs which, in turn, depend upon the most
sensitive cells. As noted previously, the most sensitive organs are the blood forming organs and the
gastrointestinal system.
The biological effects on the whole body from exposure to radiation will depend upon several factors.
Some of these are listed above. For example, a person, already susceptible to infection, who receives
a large dose of radiation may be affected by the radiation more than a healthy person.

Radiation Effects
High Doses (Acute)
Low Doses (Chronic)
Biological effects of radiation are typically divided into two categories. The first category consists of
exposure to high doses of radiation over short periods of time producing acute or short term effects. The
second category represents exposure to low doses of radiation over an extended period of time producing
chronic or long term effects.
High doses tend to kill cells, while low doses tend to damage or change them. High doses can kill so
many cells that tissues and organs are damaged. This in turn may cause a rapid whole body response
often called the Acute Radiation Syndrome (ARS). High dose effects are discussed on pages 6-12 to 6-
16.
Low doses spread out over long periods of time don’t cause an immediate problem to any body organ.
The effects of low doses of radiation occur at the level of the cell, and the results may not be observed
for many years. Low dose effects are discussed on pages 6-17 to 6-23.

Occupation High Dose Exposures
Chernobyl
Irradiators
Inadvertent Criticalities
Non-Occupational High Dose Exposures
Chernobyl (firefighters)
Nagasaki and Hiroshima
Therapy source in Goiania, Brazil
Although we tend to associate high doses of radiation with catastrophic events such as nuclear weapons
explosions, there have been documented cases of individuals dying from exposure to high doses of
radiation resulting from workplace accidents and other tragic events.
Some examples of deaths which have occurred as a result of occupational (worker related) accidents are:
Inadvertent criticality (too much fissionable material in the right shape at the wrong time)
Irradiator (accidental exposure to sterilization sources, which can be more than 10 million curies)
Chernobyl (plant workers)
An example of a nonoccupational accident occurred in 1987 in Goiania, Brazil. An abandoned medical

therapy source (cesium) was found and cut open by people who did not know what it was. This resulted
in the deaths of several members of the public and the spread of radioactive contamination over a large
area.
A recent inadvertent criticality event occurred in a fuel processing plant in Japan.

High Dose Effects
Dose (Rad) Effect Observed
15 - 25 Blood count changes in a group of people
50 Blood count changes in an individual
100 Vomiting (threshold)
150 Death (threshold)
320 - 360 LD 50/60 with minimal care
480 - 540 LD 50/60 with supportive medical care
1,100 LD 50/60 with intensive medical care (bone marrow

transplant)
Every acute exposure will not result in death. If a group of people is exposed to a whole body
penetrating radiation dose, the above effects might be observed. The information for this table was
extracted from NCRP Report No. 98, Guidance on Radiation Received in Space Activities, 1989.
In the above table, the threshold values are the doses at which the effect is first observed in the most
sensitive of the individuals exposed. The LD 50/60 is the lethal dose at which 50% of those exposed
to that dose will die within 60 days.
It is sometimes difficult to understand why some people die while others survive after being exposed
to the same radiation dose. The main reasons are the health of the individuals at the time of the exposure
and their ability to combat the incidental effects of radiation exposure, such as the increased
susceptibility to infections.

Other High Dose Effects

Skin Burns
Hair Loss
Sterility
Cataracts
Besides death, there are several other possible effects of a high radiation dose.
Effects on the skin include erythema (reddening like sunburn), dry desquamation (peeling), and moist
desquamation (blistering). Skin effects are more likely to occur with exposure to low energy gamma,
X-ray, or beta radiation. Most of the energy of the radiation is deposited in the skin surface. The dose
required for erythema to occur is relatively high, in excess of 300 rad. Blistering requires a dose in
excess of 1,200 rad.
Hair loss, also called epilation, is similar to skin effects and can occur after acute doses of about 500 rad.
Sterility can be temporary or permanent in males, depending upon the dose. In females, it is usually
permanent, but it requires a higher dose. To produce permanent sterility, a dose in excess of 400 rad is
required to the reproductive organs.
Cataracts (a clouding of the lens of the eye) appear to have a threshold of about 200 rad. Neutrons are
especially effective in producing cataracts, because the eye has a high water content, which is particularly
effective in stopping neutrons.

Acute Radiation Syndrome (ARS)
Hematopoietic
Gastrointestinal
Central Nervous System
If enough important tissues and organs are damaged, one of the Acute Radiation Syndromes could result.
The initial signs and symptoms of the acute radiation syndrome are nausea, vomiting, fatigue, and loss
of appetite. Below about 150 rad, these symptoms, which are no different from those produced by a
common viral infection, may be the only outward indication of radiation exposure.
As the dose increases above 150 rad, one of the three radiation syndromes begins to manifest itself,
depending upon the level of the dose. These syndromes are:
Syndrome Organs Affected Sensitivity
Hematopoietic Blood forming organs Most sensitive

Gastrointestinal Gastrointestinal system Very sensitive
Central Nervous System Brain and muscles Least sensitive

Summary of Biological Response to High Doses of Radiation
< 5 rad - No immediate observable effects
~ 5 rad to 50 rad - Slight blood changes may be detected by medical evaluations
~ 50 rad to 150 - Slight blood changes will be noted and symptoms of nausea,
rad fatigue, vomiting, etc. likely
~ 150 rad to - Severe blood changes will be noted and symptoms appear
1,100 rad immediately. Approximately 2 weeks later, some of those
exposed may die. At about 300 - 500 rad, up to one half of the
people exposed will die within 60 days without intensive medical
attention. Death is due to the destruction of the blood forming
organs. Without white blood cells, infection is likely. At the
lower end of the dose range, isolation, antibiotics, and
transfusions may provide the bone marrow time to generate new
blood cells and full recovery is possible. At the upper end of the
dose range, a bone marrow transplant may be required to produce
new blood cells.
~ 1,100 rad to - The probability of death increases to 100% within one to two
2,000 rad weeks. The initial symptoms appear immediately. A few days
later, things get very bad, very quickly since the gastrointestinal
system is destroyed. Once the GI system ceases to function,
nothing can be done, and medical care is for comfort only.
> 2,000 rad - Death is a certainty. At doses above 5,000 rad, the central
nervous system (brain and muscles) can no longer control the
body functions, including breathing blood circulation.
Everything happens very quickly. Nothing can be done, and
medical care is for comfort only.
As noted, there is nothing that can be done if the dose is high enough to destroy the gastrointestinal or
central nervous system. That is why bone marrow transplants don’t always work.
In summary, radiation can affect cells. High doses of radiation affect many cells, which can result in
tissue/organ damage, which ultimately yields one of the Acute Radiation Syndromes. Even normally
radio-resistant cells, such as those in the brain, cannot withstand the cell killing capability of very high
radiation doses. The next few pages will discuss the biological effects of low doses of radiation.

Annual Exposure to Average U.S. Citizen

Exposure Source Average Annual Effective Dose Equivalent
(millirems)
Natural:
Radon 200
Other 100
Occupational 0.90
Nuclear Fuel Cycle 0.05
Consumer Products:
Tobacco ?*
Other 5 - 13
Environmental Sources 0.06
Medical:
Diagnostic X-rays 39
Nuclear Medicine 14
Approximate Total 360
* The whole body dose equivalent from tobacco products is difficult to determine. However, the dose to a portion of the
lungs is estimated to be 16,000 millirems/year.
Everyone in the world is exposed continuously to radiation. The average radiation dose received by the
United States population is given in the table above. This data was extracted from material contained
in NCRP Report No. 93, Ionizing Radiation Exposure of the Population of the United States, 1987.
Radiation workers are far more likely to receive low doses of radiation spread out over a long period of
time rather than an acuate dose as discussed previously. The principal effect of low doses of radiation
(below about 10 rad) received over extended periods of time is non-lethal mutations, with the greatest
concern being the induction of cancer.
The next few pages will discuss the biological effects of low doses of radiation.

Categories of Effects of Exposure to

Low Doses of Radiation
Genetic
Somatic
In-Utero
There are three general categories of effects resulting from exposure to low doses of radiation. These
are:
Genetic - The effect is suffered by the offspring of the individual exposed.
Somatic - The effect is primarily suffered by the individual exposed. Since cancer is the
primary result, it is sometimes called the Carcinogenic Effect.
In-Utero - Some mistakenly consider this to be a genetic consequence of radiation exposure,

because the effect, suffered by a developing embryo/fetus, is seen after birth.
However, this is actually a special case of the somatic effect, since the embryo/fetus
is the one exposed to the radiation.

Genetic Effects
Mutation of the reproductive cells passed on to
the offspring of the exposed individual
The Genetic Effect involves the mutation of very specific cells, namely the sperm or egg cells.
Mutations of these reproductive cells are passed to the offspring of the individual exposed.
Radiation is an example of a physical mutagenic agent. There are also many chemical agents as well
as biological agents (such as viruses) that cause mutations.
One very important fact to remember is that radiation increases the spontaneous mutation rate, but does
not produce any new mutations. Therefore, despite all of the hideous creatures supposedly produced by
radiation in the science fiction literature and cinema, no such transformations have been observed in
humans. One possible reason why genetic effects from low dose exposures have not been observed in
human studies is that mutations in the reproductive cells may produce such significant changes in the
fertilized egg that the result is a nonviable organism which is spontaneously resorbed or aborted during
the earliest stages of fertilization.
Although not all mutations would be lethal or even harmful, it is prudent to assume that all mutations
are bad, and thus, by USNRC regulation (10 CFR Part 20), radiation exposure SHALL be held to the
absolute minimum or As Low As Reasonably Achievable (ALARA). This is particularly important since
it is believed that risk is directly proportional to dose, without any threshold.

Somatic Effects
Effect is suffered by the individual exposed
Primary consequence is cancer
Somatic effects (carcinogenic) are, from an occupational risk perspective, the most significant since the
individual exposed (usually the radiation worker) suffers the consequences (typically cancer). As noted
in the USNRC Regulatory Guide 8.29, this is also the NRC’s greatest concern.
Radiation is an example of a physical carcinogenic, while cigarettes are an example of a chemical cancer
causing agent. Viruses are examples of biological carcinogenic agents.
Unlike genetic effects of radiation, radiation induced cancer is well documented. Many studies have
been completed which directly link the induction of cancer and exposure to radiation. Some of the
population studied and their associated cancers are:
Lung cancer - uranium miners

Bone cancer - radium dial painters
Thyroid cancer - therapy patients
Breast cancer - therapy patients
Skin cancer - radiologists
Leukemia - bomb survivors, in-utero exposures, radiologists, therapy patients

In-Utero Effects
Effects of radiation on embryo/fetus
Intrauterine Death
Growth Retardation
Developmental Abnormalities
Childhood Cancers
The in-utero effect involves the production of malformations in developing embryos.
Radiation is a physical teratogenic agent. There are many chemical agents (such as thalidomide) and
many biological agents (such as the viruses which cause German measles) that can also produce
malformations while the baby is still in the embryonic or fetal stage of development.
The effects from in-utero exposure can be considered a subset of the general category of somatic effects.
The malformation produced do not indicate a genetic effect since it is the embryo that is exposed, not
the reproductive cells of the parents.
The actual effects of exposure in-utero that will be observed will depend upon the stage of fetal
development at the time of the exposure:
Weeks Post Conception Effect
0 - 1 (preimplantation) Intrauterine death

2 - 7 (organogenesis) Developmental abnormalities/growth retardation/cancer
8 - 40 (fetal stage) Same as above with lower risk plus possible functional abnormalities

Radiation Risk:
With any exposure to radiation, there is some risk
The approximate risks for the three principal effects of exposure to low levels of radiation are:
Effect Excess Cases per 10,000 exposed per rad
Genetic 2 to 4
Somatic (cancer) 4 to 20
In-Utero (cancer) 4 to 12
In-Utero (all effects) 20 to 200
Genetic - Risks from 1 rem of radiation exposure to the reproductive organs are approximately 50
to 1,000 times less than the spontaneous risk for various anomalies.
Somatic - For radiation induced cancers, the risk estimate is small compared to the normal
incidence of about 1 in 4 chances of developing any type of cancer. However, not all
cancers are associated with exposure to radiation. The risk of dying from radiation
induced cancer is about one half the risk of getting the cancer.
In-Utero - Spontaneous risks of fetal abnormalities are about 5 to 30 times greater than the risk of
exposure to 1 rem of radiation. However, the risk of childhood cancer from exposure in-
utero is about the same as the risk to adults exposed to radiation. By far, medical practice
is the largest source of in-utero radiation exposure.
Because of overall in-utero sensitivity, the NRC, in 10 CFR Part 20, requires that for the declared
pregnant woman, the radiation dose to the embryo/fetus be maintained less than or equal to 0.5 rem
during the entire gestation period. This limit is one-tenth of the annual dose permitted to adult radiation
workers. This limit applies to the worker who has voluntarily declared her pregnancy in writing. For
the undeclared pregnant woman, the normal occupational limits for the adult worker apply (as well as
ALARA).

Linear No-Threshold Risk Model
RISK
0 DOSE
General consensus among experts is that some radiation risks are related to radiation dose by a linear,
no-threshold model. This model is accepted by the NRC since it appears to be the most conservative.
LINEAR - An increase in dose results in a proportional increase in risk

NO-THRESHOLD - Any dose, no matter how small, produces some risk
The risk does not start at 0 because there is some risk of cancer, even with no occupational exposure.
The slope of the line just means that a person that receives 5 rems in a year incurs 10 times as much risk
as a person that receives 0.5 rems in a year.
Exposure to radiation is not a guarantee of harm. However, because of the liner, no-threshold model,
more exposure means more risk, and there is no dose of radiation so small that it will not have some
effect.

Review of Radiation Oncology Physics: A Handbook for Teachers and Students
CHAPTER 14.
BASIC RADIOBIOLOGY
NAGALINGAM SUNTHARALINGAM
Department of Radiation Oncology
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, U.S.A.
ERVIN B. PODGORSAK
Department of Medical Physics
McGill University Health Centre
Montréal, Québec, Canada
JOLYON H. HENDRY
Applied Radiation Biology and Radiotherapy Section
Department of Nuclear Sciences and Applications
International Atomic Energy Agency
Vienna, Austria
14.1. INTRODUCTION
Radiobiology, a branch of science that deals with the action of ionizing radiation on
biological tissues and living organisms, is a combination of two disciplines: radiation physics
and biology. All living things are made up of protoplasm that consists of inorganic and
organic compounds dissolved or suspended in water. The smallest unit of protoplasm capable
of independent existence is the cell.
• Cells contain inorganic compounds (water and minerals) as well as organic

compounds (proteins, carbohydrates, nucleic acids, lipids).
• The two main constituents of a cell are the cytoplasm, which supports all
metabolic functions within the cell, and the nucleus, which contains the genetic
information (DNA).
• Human cells are either somatic cells or germ cells.
• Cells propagate through division; division of somatic cells is called mitosis,

division of germ cells meiosis.
• When a somatic cell divides, two cells are produced, each carrying a chromosome
complement identical to that of the original cell. The new cells themselves may
undergo further division and the process continues.
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Chapter 14. Basic Radiobiology
• Somatic cells are classified as:
- Stem cells: exist to self-perpetuate and produce cells for a differentiated cell
population (e.g., stem cells of the hematopoietic system, epidermis, mucosal
lining of the intestine).
- Transit cells: cells in movement to another population (e.g., a reticulocyte
which is differentiating to become an erythrocyte).
- Mature cells: cells that are fully differentiated and do not exhibit mitotic
activity (e.g., muscle cells, nervous tissue).
• A group of cells that together perform one or more functions is referred to as

tissue.
• A group of tissues that together perform one or more functions is called an organ.
• A group of organs that perform one or more functions is a system of organs or an

organism.
14.2. CLASSIFICATION OF RADIATIONS IN RADIOBIOLOGY
For use in radiobiology and radiation protection the physical quantity that is useful for
defining the quality of an ionizing radiation beam is the linear energy transfer (LET). In
contrast to the stopping power that focuses attention on the energy loss by an energetic
charged particle moving through a medium, the LET focuses attention on the linear rate of
energy absorption by the absorbing medium as the charged particle traverses the medium.
The International Commission on Radiological Units and Measurements (ICRU) defines the
LET as follows: "LET of charged particles in a medium is the quotient dE/dl, where dE is the
average energy locally imparted to the medium by a charged particle of specified energy in
traversing a distance of dl".
In contrast to the stopping power with a typical unit of MeV/cm, the unit usually used for the
LET is keV / µ m. The energy average is obtained by dividing the particle track into equal
energy increments and averaging the length of track over which these energy increments are
deposited.
• Typical LET values for commonly used radiations are:
- 250 kVp x ray : 2 keV / µ m

- cobalt-60 gamma ray : 0.3 keV/ µ m
- 3 MeV x ray : 0.3 keV/ µ m
- 1 MeV electron : 0.25 keV/ µ m
• Values for other less commonly used radiations are:
- 14 MeV neutrons : 12 keV/ µ m

- heavy charged particles: 100-200 keV/ µ m
- 1 keV electron : 12.3 keV/ µ m
- 10 keV electron : 2.3 keV/ µ m
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X rays and gamma rays are considered low LET (sparsely ionizing) radiations, while energetic
neutrons, protons and heavy charged particles are high LET (densely ionizing) radiations. The
demarcation value between low and high LET is at about 10 keV/ µ m.
14.3. CELL CYCLE AND CELL DEATH
The cell proliferation cycle is defined by two well-defined time periods:
(1) mitosis M where division takes place, and

(2) the period of DNA synthesis S.
The S and M portions of the cell cycle are separated by two periods (gaps) G1 and G2 when
DNA is not yet synthesized but other metabolic processes take place.
• The time between successive divisions (mitoses) is called cell cycle time. For
mammalian cells growing in culture the S phase is usually in the range of 6-8
hours, M less than an hour, G2 in the range of 2-4 hours, and G1 from 1-8 hours,
making the total cell cycle in the order of 10-20 hours. In contrast, the cell cycle
for stem cells in certain tissues is up to about 10 days.
• In general, cells are most radiosensitive in the M and G2 phases, and most resistant
in the late S phase.
• The cell cycle time of malignant cells is shorter than that of some normal tissue
cells, but during regeneration after injury normal cells can proliferate faster.
• Cell death for non-proliferating (static) cells is defined as the loss of a specific
function, while for stem cells it is defined as the loss of reproductive integrity
(reproductive death). A surviving cell that maintains its reproductive integrity and
proliferates indefinitely is said to be clonogenic.
14.4. IRRADIATION OF CELLS
When cells are exposed to ionizing radiation the standard physical effects between radiation
and atoms or molecules of the cells occur first and the possible biological damage to cell
functions follows later. The biological effects of radiation result mainly from damage to the
DNA which is the most critical target within the cell; however, there are also other sites in the
cell which, when damaged, may lead to cell death. When directly ionizing radiation is
absorbed in biological material, the damage to the cell may occur in one of two ways: direct
or indirect action.
14.4.1. Direct action in cell damage by radiation
In direct action the radiation interacts directly with the critical target in the cell. The atoms of
the target itself may be ionized or excited through Coulomb interactions leading to the chain
of physical and chemical events that eventually produce the biological damage. Direct action
is the dominant process in interaction of high LET particles with biological materials.
399
14.4.2. Indirect action of cell damage by radiation
In indirect action the radiation interacts with other molecules and atoms (mainly water, since
80% of a cell is composed of water) within the cell to produce free radicals that can, through
diffusion in the cell, damage the critical target within the cell. In interactions of radiation with
water short-lived yet extremely reactive free radicals such as H2O+ (water ion) and OH•
(hydroxyl radical) are produced. The free radicals in turn can cause damage to the target
within the cell.
• The free radicals that break the chemical bonds and produce chemical changes
that lead to biological damage are highly reactive molecules because they have an
unpaired valence electron.
• About two thirds of the biological damage by low LET radiations (sparsely
ionizing radiations), such as x-rays or electrons, is due to indirect action.
• The indirect action can be modified by chemical sensitisers or radiation pro-

tectors.
• For the indirect action of x-rays the steps involved in producing biological
damage are as follows:
Step 1: Primary photon interaction (photoelectric effect, Compton effect, pair

production) produces a high energy electron.
Step 2: The high-energy electron in moving through tissue produces free

radicals in water.
Step 3: The free radicals may produce changes in DNA from breakage of
chemical bonds.
Step 4: The changes in chemical bonds result in biological effects.
Step (1) is in the realm of physics; step (2) in chemistry; steps (3) and (4) in radiobiology.
14.4.3. Fate of irradiated cells
Irradiation of a cell will result in one of the following four possible outcomes:
(1) No effect
(2) Division delay: the cell is delayed from going through division.
(3) Apoptosis: the cell dies before it can divide or afterwards by fragmentation into
smaller bodies which are taken up by neighbouring cells.
(4) Reproductive failure: the cell dies when attempting the first or subsequent mitosis.
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14.5. TYPE OF RADIATION DAMAGE
14.5.1. Time scale
The time scale involved between the breakage of chemical bonds and the biological effect
may be hours to years, depending on the type of damage.
• If cell kill is the result, it may happen in hours to days when the damaged cell
attempts to divide (early effects of radiation).
• If the damage is oncogenic (cancer induction), then its expression may be delayed
for years (late effects of radiation).
• If the damage is a mutation in a germ cell, the effects may not be expressed for
generations.
• In addition to carcinogenesis (induction of cancer) the late effects of radiation

include: (i) life span shortening; (ii) genetic damage, and (iii) potential effects to
the fetus. Ionizing radiation has been proven to cause leukemia and has been
implicated in development of many other cancers in tissues such as bone, lung,
skin, thyroid and breast.
14.5.2. Classification of radiation damage
Radiation damage to mammalian cells is divided into three categories:
(1) Lethal damage is irreversible, irreparable, and leads to cell death;
(2) Sublethal damage can be repaired in hours unless additional sublethal damage is
added and eventually leads to lethal damage; and
(3) Potentially lethal damage can be manipulated by repair when cells are allowed to
remain in a non-dividing state.
14.5.3. Somatic and genetic effects
The effects of radiation on the human population can be classified as either somatic or
genetic.
• Somatic effects are harm that exposed individuals suffer during their lifetime, such
as radiation-induced cancers (carcinogenesis), sterility, opacification of the eye
lens, and life shortening.
• Genetic or hereditary effects are radiation-induced mutations to an individual's

genes and DNA that can contribute to the birth of defective descendants.
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Carcinogenesis expresses itself as a late somatic effect in the form of acute or chronic
myeloid leukemia or some solid tumours, for example, in skin, bone, lung, thyroid or breast.
Human data on carcinogenesis have been collected from the following sources:
(1) Low level occupational exposure.

(2) Atomic bomb survivors in Hiroshima and Nagasaki.
(3) Medical radiation exposure to patients (for example, treatment of ankylosing
spondylitis, treatment of thyroid abnormalities, radiotherapy of cancer) and staff
(for example, radiologists in the early part of last century).
14.5.4. Stochastic and deterministic (non-stochastic) effects
The harmful effects of radiation may be classified into two general categories: stochastic and
deterministic (non-stochastic). The NCRP defines these effects as follows:
• A stochastic effect is one in which the probability of occurrence increases with

increasing dose but the severity in affected individuals does not depend on the
dose (induction of cancer, i.e., radiation carcinogenesis, genetic effects). There is
no threshold dose for effects that are truly stochastic.
• A deterministic (non-stochastic) effect is one which increases in severity with

increasing dose, usually above a threshold dose, in affected individuals (organ
atrophy, fibrosis, lens opacification, blood changes, decrease in sperm count).
14.5.5. Acute vs. chronic effects
An organ or tissue expresses response to radiation damage either as an acute effect or as late
(chronic) effect.
• Acute effects manifest themselves soon after exposure to radiation and are
characterized by inflammation, edema, denudation of epithelia and hemorrhage.
• Chronic effects are delayed and are characterized by fibrosis, atrophy, ulceration,
stenosis or obstruction of the intestine.
14.5.6. Total body radiation response
The response of an organism to acute total body radiation exposure is influenced by the
combined response to radiation of all organs constituting the organism. Depending on the
actual total body dose above 1 Gy, the response is described as a specific radiation syndrome:
- 1 Gy < Dose < 10 Gy: bone marrow syndrome

- 10 Gy < Dose < 100 Gy: gastrointestinal (GI) syndrome
- Dose > 100 Gy: central nervous system (CNS) syndrome
402
Human data on specific radiation syndromes have been collected from the following sources:
- Accidents in industry and research laboratories

- Accidents involving exposure from radioactive fallout from nuclear testing of
weapons or the Chernobyl nuclear power plant accident
- Exposure of humans to high levels of radiation in Hiroshima and Nagasaki
- Medical exposure of humans to total body irradiations
14.5.7. Fetal irradiation
Between conception and birth the fetus passes through three basic stages of development:
- pre-implantation (day: 1 to 10);

- organogenesis (day: 11 to 42); and
- growth stage (day: 43 to birth).
Radiation is a known teratogen (i.e., it causes birth defects).
• The effects of radiation on the fetus depend on two factors: dose and stage of
development at the time of exposure.
• The principal effects of radiation on a fetus are: fetal or neonatal death, malfor-
mations, growth retardation, congenital defects, and cancer induction.
• An abortion to avoid a possibility of radiation-induced congenital abnormalities

should be considered only when the fetal dose has exceeded 10 cGy. For doses
exceeding 25 cGy an abortion is recommended.
14.6. CELL SURVIVAL CURVES
A cell survival curve describes the relationship between the surviving fraction of cells, i.e.,
the fraction of irradiated cells that maintain their reproductive integrity (clonogenic cells), and
the absorbed dose.
• Cell survival as a function of radiation dose is graphically represented by plotting

the surviving fraction on a logarithmic scale on the ordinate against dose on a
linear scale on the abscissa.
• Cell surviving fractions are determined with in-vitro or in-vivo techniques.

Examples of survival curves for irradiation of cells by densely (A) and sparsely
(B) ionizing radiation beams are sketched in Fig. 14.1.
The type of radiation influences the shape of the cell survival curves. Densely ionizing
radiations exhibit a cell survival curve that is almost an exponential function of dose, shown
by almost a straight line on the log-linear plot. For sparsely ionizing radiation, on the other
hand, the curves show an initial slope followed by a shoulder region and then become nearly
straight at higher doses. Factors that make cells less radiosensitive are: removal of oxygen to
hypoxic state, the addition of chemical radical-scavengers, the use of low dose-rates or
multifractionated irradiation, and cells synchronized in the late-S phase of the cell cycle.
403
FIG. 14.1. Sketch of typical cell survival curves for (A) high LET (densely ionizing) radiation
and (B) low LET (sparsely ionizing) radiation.
Several mathematical methods of varying degrees of complexity have been developed to

define the shape of cell survival curves, all based on the concept of random nature of energy
deposition by radiation.
• The linear-quadratic model is now most often used to describe the cell survival
curve assuming that there are two components to cell kill by radiation:
−α D −βD 2
S(D) = e , (14.1)
where
S(D) is the fraction of cells surviving a dose D,

α is a constant describing the initial slope of the cell survival curve, and
β is a smaller constant describing the quadratic component of cell killing.
• The ratio α / β gives the dose at which the linear and quadratic components of
cell killing are equal.
• For completeness, the earlier multi-target single-hit model described the slope of
the survival curve by Do (the dose to reduce survival to 37% of its value at any
point on the final near-exponential portion of the curve) and the extrapolation
number (the point of intersection of the slope on the log-survival axis). However,
this model does not have any current biological basis.
404
14.7. DOSE-RESPONSE CURVES
A plot of a biological effect observed (e.g., tumour induction, tissue response) against the
dose given is called a dose-response curve. Generally, as dose increases so does the effect.
• Three types of dose-response relationships are known:
- Linear;
- Linear-quadratic;
- Sigmoid.
• The dose-response curves may or may not have a threshold. A threshold dose is
the largest dose for a particular effect studied, below which no effect will be
observed.
Various dose response curves are sketched in Fig.14.2 with:
(A) linear relationship-no threshold;

(B) linear relationship with threshold;
(C) linear-quadratic relationship-no threshold;
(D) linear relationship (area below the dashed line indicates natural incidence of the
effect);
(E) sigmoid relationship with threshold.
FIG. 14.2. Sketch of typical dose response curves for cancer induction (curves A, B, C, D)
and for tissue response (curve E). Curve (A) represents linear relationship - no threshold;
curve (B) linear relationship with threshold DT; curve (C) linear-quadratic relationship - no
threshold (assumed for stochastic effects, e.g., carcinogenesis); curve (D) linear relationship-
no threshold (area below dashed line represents the natural incidence of the effect, e.g.,
carcinogenesis); and curve (E) sigmoid relationship with threshold D1, as is common for
deterministic effects in tissues, e.g., tumour control, treatment morbidity.
405
The response of different tissues or organs to radiation varies markedly, depending primarily
on two factors:
(1) Inherent sensitivity of the individual cells

(2) Kinetics of the population.
There is a clear distinction in radiation response between tissues that are early responding
(skin, mucosa, intestinal epithelium) and those that are late responding (spinal cord), as
shown schematically in Fig. 14.3 for the surviving fraction against the dose.
• The cell survival curves for the late responding tissues are more curved than those
for the early responding tissues.
• For early effects the ratio α / β is large and α dominates at low doses.
• For late effects α / β is small and β has an influence even at low doses.
• The two components for mammalian cell killing are equal at approximately 10 Gy
and 2 Gy for early and late effects, respectively.
FIG. 14.3. Sketch of typical cell survival curves for (A) early responding tissues and (B) for
late responding tissues.
406
14.8. MEASUREMENT OF RADIATION DAMAGE IN TISSUE
The effects of radiation on tissue as a function of dose is measured with assays and the
measurement results are given in the form of cell survival curves or dose response curves.
Three categories of tissue assays are in use:
(1) Clonogenic assays measure the reproductive integrity of the clonogenic stem cells
in tissue and the measurements result in cell survival curves.
(2) Functional assays measure functional end-points for various tissues and produce
dose response curves, where the response is measured on a graded reaction scale
or expressed as a proportion of cases where reactions are greater than a specified
level.
(3) Lethality assays quantify the number of animal deaths after irradiation of a
specific organ with a given dose. The experiments usually result in deduced
values of the parameter LD50 defined as the (lethal) dose to a specific organ that
kills 50% of the animals.
14.9. NORMAL AND TUMOUR CELLS: THERAPEUTIC RATIO
The aim of radiotherapy is to deliver enough radiation to the tumour to destroy it without
irradiating normal tissue to a dose that will lead to serious complications (morbidity). As
shown in Fig. 14.4, the principle is usually illustrated by plotting two sigmoid curves, one for
the tumour control probability (TCP, curve A) and the other for normal tissue complication
probability (NTCP, curve B).
FIG. 14.4. The principle of therapeutic ratio. Curve (A) represents the tumour control
probability, curve (B) the probability of complications. The total dose is delivered in 2 Gy
fractions.
407
• The optimum choice of radiation dose delivery technique in treatment of a given

tumour is such that it maximizes the TCP and simultaneously minimizes the
NTCP. For a typical radiotherapy treatment, TCP ≥ 0.5 and NTCP ≤ 0.05.
• The farther is curve B (NTCP) to the right of curve A (TCP) in Fig. 15.4, the
easier it is to achieve the radiotherapeutic goal, the larger is the so-called
therapeutic ratio, and the less likely will be that the treatment causes
complications.
• The therapeutic ratio generally refers to the ratio of TCP and NTCP at a specified
dose level; however, it is also often defined as the ratio of doses at a specified
level of response (usually 0.05) for normal tissue.
• Figure 14.4 shows an ideal situation; in reality, the NTCP curve is often shallower
than the NTCP curve. Moreover, the TCP curve in certain tumours never reaches
a value of 1.0 as a result of microscopic or metastatic spread of the disease beyond
the primary tumour site. It is thus imperative that the average doses to normal
tissues be kept lower than the doses to tumours in order to minimize treatment
complications and optimize treatment outcomes. In modern radiotherapy this is
achieved through sophisticated 3-dimensional treatment planning (forward or
inverse) and dose delivery (conformal or intensity-modulated).
• In the early days of radiotherapy it was usually assumed that normal cells were
less sensitive to radiation than tumour cells; however, currently it is accepted that
both malignant and normal mammalian cells responsible for early reactions
exhibit similar values for Do around 1.3 Gy.
• It is for late reactions that the shoulder on the cell survival curve is effectively
greater than it is for tumours or early-reacting tissues, so providing a differential
that is exploited in hyperfractionation protocols.
• The therapeutic ratio varies with many factors, such as the dose-rate and LET of
the irradiation, the presence of radiosensitizers or radioprotectors, the design of
treatment plan, and the precision of implementation of the treatment plan.
14.10. OXYGEN EFFECT
The presence or absence of molecular oxygen within a cell influences the biological effect of
ionizing radiation: the larger the cell oxygenation above anoxia, the larger is the biological
effect until saturation of the effect of oxygen occurs, especially for low LET radiations. As
shown in Fig. 14.5, the effect is quite dramatic for low LET (sparsely ionizing) radiations,
while for high LET (densely ionizing) radiations it is much less pronounced. The ratio of
doses without and with oxygen (hypoxic vs. well-oxygenated cells) to produce the same
biological effect is called the oxygen enhancement ratio (OER).
Dose to produce a given effect without oxygen

OER = (14.2)
Dose to produce the same effect with oxygen
408
FIG. 14.5. Typical cell surviving fractions for x rays, neutrons and α particles: dashed
curves are for well oxygenated cells, solid curves for hypoxic cells.
FIG. 14.6. Oxygen enhancement ratio (OER) against LET. The vertical dashed line separates
the low LET region where LET <10 µm from the high LET region where LET > 10 µm.
• The OER for x-rays and electrons is about 3 at high doses and falls to about 2 for
doses of 1 to 2 Gy.
• The OER decreases as the LET increases and approaches OER = 1 at about LET =
150 keV/µ m , as sketched in Fig. 14.6.
• Reoxygenation is the process by which cells that are hypoxic during irradiation
become oxygenated afterwards.
409
14.11. RELATIVE BIOLOGICAL EFFECTIVENESS
As the LET of radiation increases, the ability of the radiation to produce biological damage
also increases. Relative biological effectiveness (RBE) compares the dose of test radiation to
the dose of standard radiation to produce the same biological effect. The standard radiation is
usually taken as 250 kVp x rays for historical reasons. RBE is defined by the following ratio:
Dose from s tan dard radiation to produce a given bio log ical effect
RBE = . (14.3)
Dose from test radiation to produce the same bio log ical effect
• RBE varies not only with type of radiation but also with type of cell or tissue,
biologic effect under investigation, dose rate and fractionation.
• In general, RBE increases with LET to reach a maximum RBE of 3 to 8

(depending on the level of cell kill) at LET ≈ 200 keV/µ m and then decreases, as
sketched in Fig. 14.7.
• An increase in the RBE in itself offers no therapeutic advantage, unless there is a

differential effect making the RBE for normal tissue smaller than that for the
tumour, increasing the relative level of tumour cell killing and the therapeutic
ratio.
FIG. 14.7. Relative biological effectiveness (RBE) against LET. The vertical dashed line
separates the low LET region where RBE ≈ 1 from the high LET region where RBE first rises
with LET, reaches a peak of about 8 for LET ≈ 200 keV/µ m and then drops with a further
increase in LET.
410
14.12. DOSE RATE AND FRACTIONATION
For the same radiation dose, radiation delivered at a lower dose rate may produce less cell
killing than radiation delivered at a higher dose rate because sublethal damage repair occurs
during the protracted exposure. As the dose rate is reduced, the slope of the survival curve
becomes shallower and the shoulder tends to disappear, since in the linear-quadratic model α
does not change significantly; however, β → 0 .
The typical dose rates used in radiotherapy are of the order of:
- 1 Gy/min in standard radiotherapy and high dose rate (HDR) brachytherapy

- 0.1 Gy/min in total body irradiation
- 0.01 Gy/min in low dose rate (LDR) brachytherapy
Fractionation of radiation treatment so that it is given over a period of weeks rather than in a
single session results in a better therapeutic ratio. However, to achieve a desired level of
biological damage the total dose in a fractionated treatment must be much larger than that in a
single treatment.
The basis of fractionation is rooted in five primary biologic factors called the five Rs of
radiotherapy:
(1) Radiosensitivity. Mammalian cells have different radiosensitivities.
(2) Repair. Mammalian cells can repair radiation damage. This is a complex process
that involves repair of sublethal damage by a variety of repair enzymes and
pathways.
(2) Repopulation. Cells repopulate while receiving fractionated doses of radiation.
(3) Redistribution in proliferating cell population throughout the cell cycle increases
the cell kill from fractionated treatment relative to single session treatment.
(4) Reoxygenation of hypoxic cells during a fractionated course of treatment, making

them more radiosensitive to subsequent doses of radiation.
Conventional fractionation is explained as follows: dividing of dose into multiple fractions

spares normal tissues through a repair of sub-lethal damage between dose fractions and
repopulation of cells. The former is greater for late-reacting tissues, and the latter for early-
reacting tisues. Concurrently, fractionation increases tumour damage through reoxygenation
and redistribution of tumour cells. A balance is achieved between the response of tumour and
early- and late-reacting normal tissues, so that small doses per fraction spare late reactions
preferentially, and a reasonable schedule-duration allows regeneration of early-reacting
tissues and tumour reoxygenation to likely occur.
The current standard fractionation is based on 5 daily treatments per week and the total
treatment time of several weeks. This regimen reflects practical aspects of dose delivery to a
patient, successful outcome to patient treatments, and convenience to staff delivering the
treatment.
411
Other fractionation schemes are studied with the aim of improving the therapeutic ratio. Some
of these are: hyperfractionation, accelerated fractionation, and CHART.
• Hyper-fractionation uses more than one fraction per day with a smaller dose per
fraction (<1.8 Gy) to reduce long-term complications and to allow delivery of
higher total tumour dose.
• Accelerated fractionation reduces the overall treatment time minimizing tumour

cell proliferation during the course of treatment.
• CHART (continuous hyper-fractionated accelerated radiotherapy) is an experi-

mental program used with 3 fractions per day, for 12 continuous days.
14.13. RADIOPROTECTORS AND RADIOSENSITIZERS
Various chemical agents may alter the cell response to ionizing radiation, either reducing or
enhancing the cell response.
• Chemical agents that reduce cell response to radiation are called radioprotectors.
They generally influence the indirect effects of radiation by scavenging the
production of free radicals. The dose modifying factor (DMF) is defined as
follows:
Dose to produce an effect with radioprotector

DMF = . (14.4)
Dose to produce same effect without radioprotector
• Chemical agents that enhance the cell response to radiation are called radio-
sensitizers generally promoting both the direct and indirect effects of radiation.
Examples are halogenated pyrimidines that intercalate between the DNA strands
and inhibit repair, and hypoxic cell radiosensitisers which act like oxygen.
• Another type of radiosensitizer are compounds containing boron that enhances the
effects of thermal neutron radiation therapy. Boron-10 has a high cross-section for
reaction with thermal neutrons (kinetic energy of the order of 0.025 eV). When a
thermal neutron interacts with boron-10, an unstable nuclide boron-11 is formed
that undergoes fission and produces α particles delivering a high dose in the
immediate vicinity of the compound that contains boron. The boron neutron
capture therapy (BNCT) has been investigated since the 1950s; however, suc-
cessful clinical applications have so far been elusive.
BIBLIOGRAPHY
HALL, E. J., “Radiobiology for the radiologist”, Lippincott, Philadelphia, Pennsylvania,

U.S.A. (2000).
NIAS, A.W.,“An introduction to radiobiology”, Wiley, New York, New York, U.S.A. (1998).
STEEL, GG., “Basic clinical radiobiology”, Arnold, London, United Kingdom (2002).
412

Lecture _ 2_
Bioradiation
1- Radiation Biology — Mechanisms
Radiobiology (also known as radiation biology), as a field of
clinical and basic medical sciences, originated from Leopold Freund's
1896 demonstration of the therapeutic treatment of a hairy mole using a
new type of electromagnetic radiation called x-rays, which was
discovered 1 year previously by the German physicist, Wilhelm Röntgen.
At the same time, Pierre and Marie Curie discovered the radioactive
polonium and radium later used to treat cancer. In simplest terms,
radiobiology is the study of the action of ionizing radiation on living
things

(Figure 1) Radia on Biology – Mechanism
The absorption of radiation energy initiates a large number of processes
in a cell. It may take some time (weeks, months and years) before the
biological result can be observed. This situation must not lead us to
believe that nothing takes place in this latent period.
1

The starting point is the absorption process (Figure 2). Radiation energy
is deposited in the system and a number of “primary” products are
formed. These products (ions, excited molecules, and free radicals) are
very reactive with lifetimes in an ordinary cell of the order of a fraction
of a second. Their reactions with molecules in the cell result in
secondary processes which finally yield a macroscopic result such as
cell death, cancer or genetic change.
(Figure 2) The radiation-induced processes in a biological system.
1-1 Molecular theory of Radiation Biology
A theory that can be used to explain the biological effects of ionizing

radiation to low doses, many different LET particles, and to interactions
between radiation and chemical agents for end points such as
cytotoxicity, mutation, chromosome aberrations, and DNA damage. The
theory is based on the assumption that DNA is the target and that
double-strand breaks in it are the molecular lesions responsible for the
biological effects of radiation.
2

1-2Radiation Damage to Proteins and DNA
protein consists of amino acids bonded together in long chains called
polypeptide chains. Altogether, 20 different amino acids can be

combined in a large number of ways. Radiation damage and changes to
the different amino acids, as well as to shorter or longer peptide chains.
Many proteins are enzymes, the “workhorses” in the cell operating as
catalysts for a number of biochemical processes.(Figure 3)
1-3 Radiation damage to DNA
There are four types of DNA Damage as Follow:
1-3-1 Single strand breaks
A single strand break is simply a break in one of the sugar-phosphate

chains. This damage is usually simple to repair and, in experiments, it
has been shown that approximately 90% of the single strand breaks are
repaired in the course of one hour at 37oC.
1-3-2 Double strand breaks
This type of damage involves both strands of the DNA helix, which are
broken opposite to each other or within a distance of a few base pairs. If
you look at Figure 4, you may imagine that this damage would kill the
cell and in experiments with bacteria a correlation is found between
double strand breaks and cell death.
1-3-3 Base damage
Experiments indicate that radiation sensitivity varies from one base to

another. After an initial ionization, rapid electronic reorganizations take
3

place with the result that the damage is transported to certain regions of
the macromolecule. The base guanine is particularly sensitive.
1-3-4 Clustered damage
Clustered damage is what makes ionizing radiation quite different from

other agents that cause DNA damage.
(Figure 3 The DNA molecule with 4 common types of radiation damage
1-4 Radiation Damage to Cells
Cell death induced by radiation can be divided into two groups:
1. If a cell dies after the first mitosis it is called mitotic death or

reproductive death.
4

2. If the cell dies before reaching the first mitosis it is called interphase
death.
1-5 Radiation and Chromosomal Aberrations
The mechanisms for the formation of aberrations are not yet fully
understood. To some degree, they involve strand breaks in the DNA-
molecule. While the biological effects connected with chromosome
changes are also not fully understood, there is a correlation between
cancer induction and the incidence of aberrations. Moreover, the
formation of chromosomal changes can be used to attain information on
the radiation dose. Attempts have been made to find chromosomal
aberrations in groups of people exposed in the Chernobyl accident and
after the atmospheric nuclear tests in the1950s and 1960s(figure 5).
(Figure 4) Type of Chromosomal aberration induced by Radiation.
5

1-6 Repair Processes
Cells have repair systems. This is a necessity for survival. The crew
working on repair in our cells are enzymes. It is the job of some
enzymes to detect DNA damage while others are called upon to repair
the damage. The repair processes can be divided into three types:
A•The specific site of damage is repaired. In this case the enzymes work
right at the damaged site. The original base sequence is preserved.
B• The whole stretch of DNA containing a damaged site (or sites) is

removed and replaced, preserving the native sequence.
C• The damage is ignored during replication; it is by-passed. With luck

the correct base will be inserted or, if incorrect, it won’t matter. Because
this type of repair is error prone, it is held in reserve in case the higher
fidelity repair systems miss, or cannot cope with, the damage. For this
reason, it is aptly called“SOS” repair.(Figure 6)
(Figure 5) Repair of pyrimidine dimers in DNA. The process includes

several steps and altogether four enzyme groups
6

The repair mechanism the following steps:
1. Recognition. It is important to have enzymes that can recognize the

damage and signal for help.
2. Cutting of the DNA-strand. It is a requirement that specific enzymes,

like the endonucleases, can cut the DNA-strand in the neighborhood of
the damage.
3. The damaged part is removed and rebuilt. Exonuclease and

polymerase are key enzymes. The former cuts out the damaged part and
the later replaces it with a new undamaged part.
4. Joining. The repair is finished when the ligase enzyme joins the cut
DNA-strand back together.
The biological effects on the whole body from exposure to radiation

will depend upon several factors. Some of -these are listed below. For
example, a person, already susceptible to infection, who receives a large
dose of radiation may be affected by the radiation more than a healthy
person.
1-Total Dose
2-Type of Cell
3-Type of Radiation
4-Age of Individual
5-Stage of Cell Division
6-Part of Body Exposed
7-General State of Health
8-Tissue Volume Exposed
9-Time Interval over which Dose is received
7

Radiation Therapy Principles
Radiation and radioactivity were discovered more than 100 years ago. Since then, radiation has
become important in cancer treatment. More than half of all people with cancer will get radiation
as at least part of their cancer treatment.
Here we will help you understand what radiation therapy is, how it’s used to treat cancer, and what
some of its common side effects are. For more detailed information on the possible side effects of
radiation and how to deal with them, please see our document Understanding Radiation Therapy:
A Guide for Patients and Families.
How does radiation work to treat cancer?

Radiation is energy that is carried by waves or a stream of particles. Radiation works by damaging
the genes (DNA) in cells. Genes control how cells grow and divide. When radiation damages the
genes of a cancer cell, it can’t grow and divide any more. Over time, the cells die. This means
radiation can be used to kill cancer cells and shrink tumors.
To understand how radiation works as a treatment, it helps to know the normal life cycle of a cell.
The cell cycle goes through 5 phases, one of which is the actual splitting of the cell. When a cell
splits, or divides, into 2 cells, it’s called mitosis. This 5-phase process is controlled by proteins
known as cyclin-dependent kinases (CDKs). Because CDKs are so important to normal cell
division, they too have a number of control mechanisms.
The cell life cycle
The cell cycle

G0 = Cell rests from dividing and does its normal work in the body
G1 = RNA and proteins are made for dividing
S = Synthesis (DNA is made for new cells)
G2 = Apparatus for mitosis is built
M = Mitosis (the cell divides into 2 cells)
G0 phase (resting stage): The cell has not yet started to divide. Cells spend much of their lives in
this phase, carrying out their day-to-day body functions, not dividing or preparing to divide.
Depending on the type of cell, this stage can last for a few hours or many years. When the cell gets
the signal to reproduce (divide), it moves into the G1 phase.
G1 phase: The cell gets information that determines if and when it will go into the next phase. It
starts making more proteins to get ready to divide. The RNA needed to copy DNA is also made in
this phase. This phase lasts about 18 to 30 hours.
S phase: In the S phase, the chromosomes (which contain the genetic code or DNA) are copied so
that both of the new cells to be made will have the same DNA. This phase lasts about 18 to 20
hours.
G2 phase: More information about if and when to proceed with cell division is gathered during
this phase. The G2 phase happens just before the cell starts splitting into 2 cells. It lasts from 2
to10 hours.
M phase (mitosis): In this phase, which lasts only 30 to 60 minutes, the cell actually splits into 2
new cells that are exactly the same.
Cells and radiation

The cell cycle phase is important in cancer treatment because usually radiation first kills the cells
that are actively dividing. It doesn’t work very quickly on cells that are in the resting stage (G0) or
are dividing less often. The amount and type of radiation that reaches the cell and the speed of cell
growth affect whether and how quickly the cell will die or be damaged. The term radiosensitivity
describes how likely the cell is to be damaged by radiation.
Cancer cells tend to divide quickly and grow out of control. Radiation therapy kills cancer cells
that are dividing, but it also affects dividing cells of normal tissues. The damage to normal cells
causes unwanted side effects. Radiation therapy is always a balance between destroying the cancer
cells and minimizing damage to the normal cells.
Radiation does not always kill cancer cells or normal cells right away. It might take days or even
weeks of treatment for cells to start dying, and they may keep dying off for months after treatment
ends. Tissues that grow quickly, such as skin, bone marrow, and the lining of the intestines are
often affected right away. In contrast, nerve, breast, brain, and bone tissue show later effects. For
this reason, radiation treatment can have side effects that might not be seen until long after
treatment is over.
In the past, it was thought that once an area was treated with radiation it could not be treated with
radiation again because of damage to the normal cells in the treatment area. But research suggests
that a second course of radiation therapy can be given to some patients.
Types of radiation used to treat cancer
Radiation used for cancer treatment is called ionizing radiation because it forms ions (electrically
charged particles) in the cells of the tissues it passes through. It creates ions by removing electrons
from atoms and molecules. This can kill cells or change genes so the cells stop growing.
Other forms of radiation such as radio waves, microwaves, and light waves are called non-ionizing.
They don’t have as much energy and are not able to form ions.
Ionizing radiation can be sorted into 2 major types:
• Photons (x-rays and gamma rays), which are most widely used in cancer treatment
• Particle radiation (such as electrons, protons, neutrons, carbon ions, alpha particles, and beta
particles)
Some types of ionizing radiation have more energy than others. The higher the energy, the more
deeply the radiation can penetrate (get into) the tissues. The way a certain type of radiation
behaves is important in planning radiation treatments. The radiation oncologist (a doctor specially
trained to treat cancer patients with radiation) selects the type and energy of radiation that is most
suitable for each patient’s cancer and location.
Photon radiation
By far the most common form of radiation used for cancer treatment is a high-energy photon
beam. This comes from radioactive sources such as cobalt, cesium, or a machine called a linear
accelerator (or linac, for short). Photon beams of energy affect the cells along their path as they go
through the body to get to the cancer, pass through the cancer, and exit the body.
Particle radiation
Electron beams or particle beams are also produced by a linear accelerator. Electrons are
negatively charged parts of atoms. They have a low energy level and don’t penetrate deeply into
the body, so this type of radiation is used most often to treat the skin, tumors, and lymph nodes that
are close to the surface of the body.
Proton beams are a form of particle beam radiation. Protons are positively charged parts of atoms.
They cause less damage to tissues they pass through but are very good at killing cells at the end of
their path. Because of this, proton beams are thought to be able to deliver more radiation to the
cancer while causing fewer side effects to normal tissues. Protons are used routinely for certain
types of cancer, but still need more study in treating others.
Some of the techniques used in proton treatment can also expose the patient to neutrons (see
below). Proton beam radiation therapy requires highly specialized equipment and is not widely
available.
Neutron beams are used for some cancers of the head, neck, and prostate and for certain
inoperable tumors. A neutron is a particle in many atoms that has no charge. Neutron beam
radiation can sometimes help when other forms of radiation therapy don’t work. Few facilities in
the United States offer it, and use has declined partly because of problems getting the beams on
target. Because neutrons can damage DNA more than photons, effects on normal tissue can be
more severe. Beams must be aimed carefully and normal tissue protected. Still, neutron beams
show great promise with salivary gland cancers that can’t be cured with surgery.
Carbon ion radiation is also called heavy ion radiation because it uses a particle that is heavier
than a proton or neutron. The particle is part of the carbon atom, which itself contains protons,
neutrons, and electrons. Because it’s so heavy, it can do more damage to the target cell than other
types of radiation. As with protons, the beam of carbon ions can be adjusted to do the most damage
to the cancer cells at the end of its path. But the effects on nearby normal tissue can be more
severe. This type of radiation is only available in a few centers in the world. It can be helpful in
treating cancers that don’t usually respond well to radiation (called radioresistant).
Alpha and beta particles are mainly produced by special radioactive substances that may be
injected, swallowed, or put into the body of a person with cancer. They’re most often used in
imaging tests, but can be helpful in treating cancer. You can read more about these in the section
called “Radiopharmaceuticals”.
Goals of radiation therapy

Most types of radiation are considered local treatments because the radiation is aimed at a specific
area of the body (where there is a tumor). Only cells in that area are affected. Most forms of
radiation therapy cannot not reach all parts of the body and so may not be helpful in treating cancer
that has spread to many distant areas.
Radiation is used to treat cancer in several ways.
To cure or shrink early stage cancer

Some cancers are very sensitive to radiation. Radiation may be used by itself in these cases to
make the cancer shrink or disappear completely. Sometimes, a few cycles of chemotherapy are
given first. For other cancers, it may be used before surgery (as pre-operative or neoadjuvant
therapy) to shrink the tumor, or after surgery to prevent the cancer from coming back (this is called
adjuvant therapy).
For certain cancers that can be cured either by radiation or by surgery, radiation may be preferred
because it can sometimes preserve the organ’s function (such as that of the larynx or the anus).
In treating some types of cancer, radiation may also be used along with chemotherapy (chemo).
This is because the chemo acts as a radiosensitizer, a drug that makes the cancer cells more
sensitive to radiation. These drugs make the radiation work better. Some chemotherapy drugs
already in use (such as 5-fluorouracil or 5-FU) are known to be radiosensitizers. The drawback of
giving chemo and radiation together is that side effects tend to be worse.
In other types of cancer, it’s better to use radiation before or after chemo.
When radiation is used along with other forms of therapy, the treatment is planned by the surgeon,
medical oncologist, and radiation oncologist, as well as the patient.
To stop cancer from recurring (coming back) somewhere else
If a type of cancer is known to spread to a certain area, doctors often assume that a few cancer cells
might already have spread there, even though imaging scans (such as CT or MRI) show no tumors.
That area may be treated to keep these cells from growing into tumors. For example, people with
some types of lung cancer may get preventive (or prophylactic) radiation to the head because this
type of cancer often spreads to the brain. Sometimes, radiation to prevent future cancer can be
given at the same time that radiation is given to treat existing cancer, especially if the prevention
area is close to the tumor itself.
To treat symptoms caused by advanced cancer

Sometimes cancer spreads too far to be cured. But even some of these tumors can still be treated to
make them smaller so that the person can feel better. Radiation might help relieve symptoms such
as pain, trouble swallowing or breathing, or bowel blockages that can be caused by advanced
cancer. This is often called palliative radiation.
Who gives radiation treatments?

During your radiation therapy, you will be cared for by a team of medical professionals. Some of
the people who may be on that team are listed here.
• A radiation oncologist is a doctor specially trained to treat cancer with radiation. This doctor
will make many of the decisions about your treatment.
• The radiation physicist makes sure that the radiation equipment is working the way it should
and that it delivers the dose of radiation your doctor prescribes.
• The dosimetrist helps the doctor plan and calculate the needed number of treatments. The
dosimetrist is supervised by the radiation physicist.
• The radiation therapist or radiation therapy technologist operates the radiation equipment and
positions you for treatment.
• A radiation therapy nurse is a registered nurse with special training in cancer treatment. He or
she will be able to give you information about your radiation treatment and advice on how to
deal with any side effects you might have.
You also may need the services of a dietitian, a physical therapist, a social worker, a dentist, a
dental oncologist, or other health care professionals.
How is radiation given?

Most people think of radiation therapy as coming from a machine outside of the body, but
radiation therapy can be given in a number of ways. Sometimes radiation is given more than one
way at the same time, or different types of radiation may be given one after the other. Some ways
radiation can be given include:
• External beam radiation
• Brachytherapy or internal radiation
• Endocavitary radiation
• Radiopharmaceuticals
External beam radiation

External beam radiation is the most widely used type of radiation therapy, and it most often uses
photon beams. The radiation comes from a machine outside the body and is focused on the cancer.
It’s a lot like getting an x-ray, but for longer. This type of radiation is most often given by
machines called linear accelerators (linacs).
External beam radiation can be used to treat large areas of the body. It also can treat more than one
area, such as the main tumor and nearby lymph nodes. External radiation is usually given daily
over several weeks. It’s given in an outpatient clinic or treatment center, so you don’t have to stay
in the hospital. The radiation is aimed at the cancer, but it affects the normal tissue it passes
through on its way into and out of the body.
Special ways to deliver external beam radiation

Three-dimensional conformal radiation therapy (3D-CRT)
This technique uses imaging scan pictures and special computers to map the location of a tumor
very precisely in 3 dimensions. The patient is fitted with a plastic mold or cast to keep the body
part still during treatment. The radiation beams are matched to the shape of the tumor and
delivered to the tumor from several directions. Careful aiming of the radiation beam may help
reduce radiation damage to normal tissues and better fight the cancer by increasing the radiation
dose to the tumor. Photon beams or particles (like protons) can be used in this way. A drawback of
3D-CRT is that it can be hard to see the full extent of some tumors on imaging tests, and any part
not seen will not get treated with this therapy.
Intensity modulated radiation therapy (IMRT)
This is an advanced form of external radiation therapy. As with 3D-CRT, computer programs are
used to precisely map the tumor in 3 dimensions. But along with aiming photon beams from
several directions, the intensity (strength) of the beams can be adjusted. This gives even more
control over the dose, decreasing the radiation reaching sensitive normal tissues while delivering
higher doses to the tumor.
A variation of IMRT is called volumetric modulated arc therapy. It uses a machine (called
RapidArc®) that delivers the radiation quickly as it rotates once around the body. This allows each
treatment to be given over just a few minutes. Although this can be more convenient for the
patient, it’s not yet clear if it’s more effective than regular IMRT.
Because of its precision, it’s even more important that a person remain in the right place and be
perfectly still during treatment. A special cast or mold may be made to keep the body in place
during treatment. Again, miscalculations in tumor size and exact location can mean missed areas
will not get treated.
Because IMRT uses a higher total dose of radiation, it may slightly increase the risk of second
cancers later on. This is something researchers are looking into.
Image-guided radiation therapy (IGRT) is an option on some newer radiation machines that
have imaging scanners built into them. This advance lets the doctor take pictures of the tumor and
make minor aiming adjustments just before giving the radiation. This may help deliver the
radiation even more precisely. This might result in fewer side effects, although more research is
needed to prove this.
Intensity modulated proton therapy (IMPT) is IMRT using proton beams instead of photon
beams. Protons are parts of atoms that in theory can deliver radiation to the area that they are
aimed at (like the cancer), while doing less damage to nearby normal tissues. Still, there have been
no studies showing that proton beam radiation is better than the more common photon beam in
terms of cancer outcomes or side effects. In fact, a 2012 study of proton beam therapy used to treat
localized prostate cancer did not show fewer side effects compared to the more common photon
beam radiation. More study on this is needed. Meanwhile, IMPT is often used for tumors near
critical body structures such as the eye, the brain, and the spine.
Protons can only be sent out by a special machine called a cyclotron or synchrotron. This machine
costs millions of dollars and requires expert staff to use and maintain it. Because of this, proton
beam therapy is expensive, and very few treatment centers in the United States offer it. Many more
studies are needed to compare outcomes between proton and photon treatment so that each is used
for the cancer type for which it works best.
Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy
These use advanced image-guided techniques to deliver a large, precise dose of radiation to a
small, well-defined tumor. The term “surgery” may be confusing because no cutting is involved.
This technique is used to treat tumors that start in or spread to the brain or head and neck region. If
the radiation is given as a single dose, it’s called stereotactic radiosurgery. If the radiation is
spread out over several doses, it’s called fractionated stereotactic radiotherapy.
When the radiation is aimed at the head, a head frame or shell is used to hold the skull still and
allow for precise aiming of radiation beams.
A related term, stereotactic body radiation therapy (SBRT), is used to describe this technique
when it’s used for tumors in other parts of the body, such as the spine, liver, pancreas, kidney,
lung, and prostate.
Once the exact location of the tumor is mapped (using imaging scans), narrow radiation beams
from a machine called a Gamma Knife® are focused at the tumor from hundreds of different angles
for a short time. The process may be repeated if needed. Another approach that’s much like this
uses a movable linear accelerator controlled by a computer. Instead of delivering many beams at
once, the linear accelerator moves around to deliver radiation to the tumor from different angles.
Several machines, with names like X-Knife®, CyberKnife®, and Clinac® work in this way.
Intraoperative radiation therapy (IORT)
With this technique, radiation is given to the cancer during surgery. The radiation may be given
using a machine for external beam radiation (a linear accelerator). Another option is to place a
radioactive substance into the area that needs treatment for a short time (like brachytherapy). It’s
often used along with a course of external radiation given before or after the operation.
IORT is useful for cancers that are deep inside the body, because normal tissues can be moved
aside during surgery, exposing the cancer. After as much tumor is removed as possible, one large
dose of radiation is directed straight at the cancer without going through normal tissues. Shielding
can also be used to protect the nearby normal tissues further. IORT is given in a special operating
room lined with radiation-shielding walls.
IORT is most often used for abdominal (belly area) or pelvic cancers that cannot be completely
removed (such as those that have grown close to vital body parts) and for cancers that tend to grow
back after treatment. This technique is not widely available.
Electromagnetic-guided radiation therapy
This is another way of aiming the radiation beam that can be used with 3D and IMRT. It uses tiny
electromagnetic implants (called transponders) that are placed into the area being treated. These
implants send out radio waves to tell the radiation therapy machines where to aim. This lets the
machine compensate for movement (like during breathing) and may allow less radiation to go to
normal tissues. It helps to refocus radiation beams as organs shift or cancer shrinks over time. It’s
sometimes known as 4-D therapy, because it includes time in the radiation planning formula. One
such system is marketed under the brand name Calypso®. In theory, better focusing radiation could
lower side effects. So far, though, this has not shown in studies to be better for patients than other
approaches.
Treatment planning for external beam radiation

The process of planning external beam radiation therapy has many steps and may take several days
to complete. But it’s required for the success of your radiation treatment. The radiation team will
design a treatment just for you. The treatment will give the strongest dose of radiation to the cancer
while sparing normal tissue as much as possible.
The first part of treatment planning is called simulation. It’s sometimes referred to as a “marking
session.” You will be asked to lie still on a table while the health care team works out the best
treatment position for you and how to keep you in that position (tape, headrests, casts, body molds,
or foam pillows may be used). They will then mark the radiation field (also called the treatment
port), which is the exact place on your body where the radiation will be aimed. The marks may be
done with permanent markers or with tattoos that look like tiny freckles. If you don’t want to be
tattooed, ask beforehand how your radiation marking will be done and what your other options are.
Your doctor may use imaging tests to check the size of the tumor, figure out where it’s most likely
to spread, outline normal tissues in the treatment area, take measurements, and plan your
treatment. Photos may also be taken and are used to make the daily treatment set-up easier.
Through a complex process called dosimetry, computer programs are used to find out how much
radiation the nearby normal structures would be exposed to if the prescribed dose was delivered to
the cancer. The doctor and dosimetrist will work together to decide on the amount of radiation you
will get and the best ways to aim it at the cancer. They base this on the size of the tumor, how
sensitive the tumor is to radiation, and how well the normal tissue in the area can withstand the
radiation.
Dosing and treatment with external beam radiation

The total amount of radiation you will get is measured in units called Gray (Gy). Often the dose is
expressed in centigray (cGy), which is one-hundredth of a Gray.
For external radiation, the total dose is often divided into smaller doses (called fractions) that are
most often given over a number of weeks. This allows the best dose to be given with the least
damage to normal tissues. Treatments are usually given 5 days a week, for about 5 to 8 weeks.
Some cancers may be treated more often than once a day.
• Hyperfractionated radiation divides the daily dose into 2 treatment sessions without changing
the length of the treatment. In this case, you would be treated twice a day for several weeks.
• Accelerated radiation gives the total dose of radiation over a shorter period of time. In other
words, giving more frequent doses (more than once a day) to get the same total dose of
radiation; it may shorten the course of treatment by a week or two.
• Hypofractionated radiation breaks radiation into fewer doses, so that each dose is larger.
Sometimes, this could mean it’s given less often than once a day.
These types of schedules can make the radiation work better for some tumors. The down side is
that radiation side effects are seen earlier and may be worse, even though it doesn’t increase the
radiation’s late effects.
It’s important that you are in the correct position each time so the right amount of radiation will be
given to the right area. For external radiation, you might get small, long-lasting or permanent
(tattoo) marks on your skin to show where treatment is to be focused. You will need to stay very
still and in the same position during each treatment, which can last up to 30 minutes. Sometimes a
special mold or cast of the body part to be treated will be used to hold you in a certain position.
This helps make sure you’re in the right place and helps you stay still. Your health care team may
also need to make special blocks or shields to protect certain parts of your body from radiation
during treatment.
Internal radiation therapy (brachytherapy)

Internal radiation therapy is also known as brachytherapy, which means short-distance therapy.
With this method, sources of radiation are put in or near the area that needs treatment. The
radiation only travels a short distance, so there is less risk of damaging nearby normal tissues.
Brachytherapy can be used to deliver a high dose of radiation to a small area in a fairly short
period of time. It’s useful for tumors that need a high dose of radiation or are near normal tissues
that are easily hurt by radiation.
The main types of internal radiation are:
• Interstitial radiation: the radiation source is placed directly into or next to the tumor using
small pellets, seeds, wires, tubes, or containers.
• Intracavitary radiation: a container of radioactive material is placed in a cavity of the body
such as the chest, rectum, uterus, or vagina.
Ultrasound, x-rays, or CT scans are used to help the doctor put the radioactive source in the right
place. The placement can be permanent or temporary.
Permanent brachytherapy uses small containers, often called pellets or seeds, which are about
the size of a grain of rice. They are put right into the tumors using thin, hollow needles. Once in
place, the pellets give off radiation for several weeks or months. Because they are very small and
cause little discomfort, they are simply left in place after their radioactive material is used up.
Temporary brachytherapy can be high-dose rate (HDR) or low-dose rate (LDR). Either type
places cylinders, hollow needles, tubes (catheters), or fluid-filled balloons into the area to be
treated that are removed after treatment. Radioactive material can be put in these containers for a
short time and then removed. This may be done by hospital staff or the radioactive material can be
put into the device remotely by machine.
For HDR brachytherapy, the radiation source is put into place for a few minutes at a
time, and then removed. This process may be repeated twice a day for up to a week, or
once a week for a few weeks.
For LDR brachytherapy, the radiation source stays in place for up to 7 days. To keep the
implant from moving, you will need to stay in bed and lie fairly still. For this reason, you
will stay in the hospital during LDR therapy.
Treatment with internal radiation

Severe pain or illness is not likely to happen while putting in radioactive implants or the catheters,
devices, or tubes for temporary placement of radioactive materials. You may feel sleepy, weak, or
nauseated for a short time if you get anesthesia (drugs that make you sleepy) while the implant or
device is put in place. Tell the nurse if you have any unusual side effects such as burning or
sweating.
Anesthesia usually is not needed to take out temporary brachytherapy implants. Most can be taken
out right in your hospital room. (The room is specially shielded to contain the radioactivity and the
staff use mobile shields to protect themselves while handling radioactive materials.) If you had to
stay in bed during implant therapy, you might have to stay in the hospital an extra day or so after
the implant is removed just to be sure you have no problems in the area where the implants were
placed.
Once implants are removed, there is no radioactivity in your body. (See the section, “Safety for the
patient and family” for more on this.) The doctor will tell you if you should limit your physical
activity for a time. Most patients are encouraged to do as much as they can. Some people need
extra sleep or rest breaks during their first days at home, but you will probably feel stronger
quickly. The area that has been treated with an implant may be sore or sensitive for some time after
treatment.
Radioembolization
This is a special type of internal radiation that’s now used only for cancer in the liver that can’t be
surgically removed. Small radioactive beads (called microspheres) are injected into the artery that
feeds the liver tumor. Brand names for these beads include TheraSphere® and SIR-Spheres®.
Once infused, the beads lodge in blood vessels near the tumor, where they give off small amounts
of radiation to the tumor site for several days. The radiation travels a very short distance, so its
effects are limited mainly to the tumor. In some cases, it can cause ulcers in the intestine, low
white blood cell counts, lung damage, or serious damage to the normal liver cells.
Radiopharmaceuticals
Radiopharmaceuticals are drugs that contain radioactive materials called radioisotopes. They may
be put into a vein, taken by mouth, or placed in a body cavity. Depending on the drug and how it’s
given, these materials travel to various parts of the body to treat cancer or relieve its symptoms.
They put out radiation, mostly in the form of alpha and beta particles, that target the affected areas.
They’re most often used in small amounts for imaging tests, but larger doses can be used to deliver
radiation.
Treatment of bone pain

Strontium 89 (Metastron®), samarium 153(Quadramet®), and Radium- 223 (Xofigo®) are
radiopharmaceuticals that can be used for tumors that have spread to the bones (bone metastases).
Other drugs are also being studied. These medicines are given in veins (intravenously or IV), so
that they go into the blood circulation. They build up in the areas of the bone where there is cancer.
The radiation they give off kills cancer cells and eases the pain caused by bone metastases.
For cancer that has already spread to several bones, this approach can be better than trying to aim
external beam radiation at each affected bone. These drugs may be used along with external beam
radiation which is aimed at the most painful bone metastases. This combined approach has helped
many men with prostate cancer, but it has not been studied as much for use in other cancers.
Some people notice more bone pain for the first couple of days after treatment, but this is not
common. These drugs can also lower blood cell counts, especially white blood cells (which can
increase the risk of infection) and platelets (which can raise the risk of bruising or bleeding).
Treatment of thyroid cancer

The thyroid gland absorbs nearly all of the iodine in the blood. Because of this, radioactive iodine
(also known as radioiodine or iodine 131) can be used to destroy the thyroid gland and thyroid
cancer with little effect on the rest of the body. This treatment is often used after thyroid cancer
surgery to destroy any thyroid cells left behind. It’s also used to treat some types of thyroid cancer
that spread to lymph nodes and other parts of the body. For more information, please see our
document called Thyroid Cancer.
Small doses of radioiodine can be given without the patient having to be in the hospital, but the
usual treatment doses for thyroid cancer require 2 to 3 days in the hospital. Several weeks after
treatment, the radioiodine is gone from the body. At that point, doctors can check to see how well
the treatment worked.
Short-term side effects of radioiodine treatment are rare, but may include neck tenderness, nausea
and stomach irritation, tenderness of the salivary glands, and dry mouth. Large doses may cause
low blood cell counts. Men may become infertile (unable to father children) after large doses.
There may be some longer-term risks, too. Large studies have found that there may be a very slight
increase in the risk of developing other types of cancer, including leukemia, in the future.
It’s recommended that women of childbearing age avoid becoming pregnant during treatment and
for at least a year after treatment. If a woman gets pregnant more than a year after treatment, there
is no evidence of a higher risk of birth defects or miscarriage. Women treated with radioactive
iodine during their childbearing years may have slightly earlier menopause.
Phosphorus 32
This form of phosphorus (also known as P-32 or chromic phosphate P 32) is put inside brain
tumors that are cystic (hollow) to kill the tumor without hurting the healthy parts of the brain.
In the past, P-32 was given into a vein (as an IV) as a common treatment for a blood disease called
polycythemia vera. P-32 was also placed inside the abdomen (belly) as a treatment for ovarian
cancer. It’s rarely used in these ways today, because there are better drugs with fewer side effects.
Radio-labeled antibodies
Monoclonal antibodies are man-made versions of immune system proteins that attack only a
specific molecular target on certain cancer cells. Scientists have learned how to pair these
antibodies with radioactive atoms. When put into the bloodstream, the antibodies act as homing
devices. They attach only to their target, bringing tiny packets of radiation directly to the cancer.
Radio-labeled antibodies are used to treat some non-Hodgkin lymphomas, especially those that
don’t respond to other treatments. They might cause allergic reactions when first infused. They
might also lower blood cell counts, which can raise the risk of infections, bruising, or bleeding.
Safety for the patient and family

People who get any type of radiation therapy often worry the radiation poses a risk to themselves
or to others around them.
If you get external beam radiation therapy, you are NOT radioactive and do not need to take
special precautions to protect others from radiation. Treatments are given in special rooms that
contain the radiation. The radiation therapist is not in the room during the treatment but can see
you and talk with you over an intercom the whole time.
If you are given a radiopharmaceutical treatment such as radioactive iodine, it will leave your
body within a few weeks, mainly through your urine, but also through saliva, sweat, and stool. To
reduce the exposure of others, you will be asked to follow some basic instructions for the first few
days after treatment. Your health care team will tell you about specific precautions, which could
include:
• Flushing the toilet 2 to 3 times after each use
• Washing hands often with plenty of soap and water, especially after using the toilet
• Using regular eating utensils (rather than disposables), not sharing them with others, and
washing them carefully after each use
• Flushing used tissues and paper napkins rather than throwing in the trash
• Drinking plenty of fluids to help flush the radioactive substance from your body
• No kissing or sexual contact for at least a week
• Sleeping in a separate bed
• Showering every day
• Keeping a distance of one arm’s length between yourself and any others who spend more than
2 hours next to you in any 24-hour period
• Avoiding prolonged close contact with infants, children, pregnant women, and even pets
• Avoiding pregnancy or breastfeeding for a certain length of time, which will depend on the
type of treatment used
For a temporary internal radiation implant, you will need to take special precautions only while
the implant is in place to avoid exposing others to radiation. With this type of radiation, body
fluids such as urine, sweat, blood or stool are usually not radioactive and probably will not need
special handling. Your health care team will give you more specific instructions.
If you need to stay in the hospital while you are getting temporary internal radiation therapy, you
will most likely be in a private room. Although the nurses and other people caring for you will not
be able to spend a long time in your room, they will give you all of the care you need. There will
also be limits on visitors while your implant is in place. As a precaution, most hospitals do not let
pregnant women or children younger than 18 visit patients who have a radiation implant. Visitors
need to check with the staff before they come in. They may be asked to stay at least 6 feet from
your bed and stay for less than 30 minutes each day.
Permanent implants use weaker radiation, and patients can usually go home after the implant
procedure. If you have permanent implants, such as seed implants, you may need to avoid close
contact with other people for the first few days while the radiation is most active. The implant will
lose energy each day. For a few weeks or months after the implant, you may be told not to have
daily close contact with pregnant women or children for more than just a few minutes. Use of a
condom during sex is often recommended for a short time. Ask your health care team about any
special precautions you need to use at home.
Possible side effects of radiation therapy

Normal body tissues vary in their response to radiation. As with tumors, normal tissues in which
cells are quickly dividing may be affected. This causes some of the side effects of radiation
treatment. Since radiation is a local treatment, side effects depend on the area of the body being
treated. The early effects of radiation may be seen a few days or weeks after treatments have
started and may go on for several weeks after treatments have ended. Other effects may not show
up until months, or even years, later. The most common side effects are briefly discussed below.
Please see our document called Understanding Radiation Therapy: A Guide for Patients and
Families for more information and ideas on dealing with these and other radiation side effects.
For general information on managing the effects of cancer and its treatment (including
chemotherapy as well as radiation), see Caring for the Patient With Cancer at Home: A Guide for
Patients and Families.
Fatigue
Fatigue is an extreme tiredness that does not get better with rest. It’s a common effect of radiation,
but the exact cause is unknown. Sometimes tumors cause the immune system to make substances
that lead to fatigue. Fatigue may also be caused by anemia (a low red blood cell count), poor
nutrition, pain, certain drugs such as steroids or chemotherapy, depression, and stress.
There’s no single treatment for fatigue, but if a cause can be found it should be treated. For
example, if the fatigue is caused by anemia, some patients may benefit from blood transfusions or
from medicines that cause the body to make more red blood cells.
Fatigue can last for a long time after treatment is over and some people never have as much energy
as they did before treatment. Light or moderate exercise with frequent rest breaks may help to
reduce fatigue. Talk with your doctor about this and other treatments that might work for you.
You can learn more about fatigue and how to deal with it in our documents called Fatigue in
People With Cancer and Anemia in People With Cancer.
Skin changes
Radiation therapy today causes less skin damage than it did in the past, but your skin might still
show a response to treatments. During the first 2 weeks of treatment, you might notice a faint
redness. Your skin may become tender or sensitive. A few people have blistering of the outer skin
layer, with some weeping until it heals. Dryness and peeling may occur in 3 to 4 weeks. After that,
the skin over the treatment area may become darker. This is because of the effect radiation has on
the cells in the skin that produce pigment (color). You could also lose hair in the skin over the area
that is being treated.
The skin in the treatment area may also become dry and itchy. Moisturizing the skin with aloe
vera, lanolin, or vitamin E may help. But before using any skin products during treatment, ask the
radiation doctor or nurse if it’s OK. Some lotions that are safe to use after treatment ends can
actually make things worse during treatment.
Do not use perfumes, deodorants, and skin lotions that contain alcohol or perfume on the treated
area. Also avoid powders unless your doctor or nurse says they’re OK to use. Stay out of the sun as
much as you can. If you must be outdoors, wear a hat and clothes that will protect your skin. After
about a month of treatment, some people getting radiation may notice skin peeling and moist
(weeping) areas. Let your medical care team know if this happens to you.
Later effects of radiation may include thinning of the skin. The skin may feel hard, especially if
surgery has also been done in the same area. Some people may have trouble with wound healing in
the area that was treated. The skin in the treatment area may always be more sensitive to the sun,
and you should be extra careful to protect it when you are outdoors.
Mouth and throat problems

Mucositis (inflammation inside the mouth and throat) is a short-term side effect that can happen
when radiation is given to the head and neck area. It can make swallowing painful, and some
patients lose weight because they have trouble eating. It usually gets better within a few weeks
after treatments end. Dry mouth and a loss of taste can be caused by radiation damage to the
salivary glands and taste buds. Thick, sticky, rope-like saliva and swallowing problems may
develop, too. These side effects often go away after treatments end, but sometimes they don’t.
Keeping your mouth clean is important to lower your risk of infection. If your mouth becomes
painful, you may be given medicine to numb the mouth or help the pain. You may need to take it
before meals so that it’s easier to eat. Be sure to tell your doctor about any pain and if the
medicines to help it are working.
Good nutrition is important for people with cancer. If mouth pain and irritation make it hard to eat
or swallow, you may need to have a feeding tube put into your stomach for a while so you can take
in enough nourishment. Your health care team will help you develop a plan to manage your
symptoms. For more suggestions, see our document, Nutrition for the Person With Cancer During
Treatment: A Guide for Patients and Families.
Radiation to the head and neck area can affect your teeth, too, and increase your chances of getting
cavities. Mouth care to prevent problems will be an important part of your treatment. Before
starting radiation, talk to your dentist and have a complete check-up. Also ask your dentist to talk
to your radiation oncologist before your radiation treatments begin, and be sure to discuss your
daily mouth care routine with the doctor or dentist. Any dental work you need may have to be done
before radiation begins and daily fluoride treatments may be prescribed to help protect your teeth.
Side effects of radiation to specific areas

Brain
Radiation therapy to large areas of the brain can sometimes cause changes in brain function that
can lead to memory loss, lower sexual desire, or poor tolerance for cold weather. Nausea, unsteady
walking, and changes in vision may also be noticed. Usually these symptoms are minor compared
to those caused by a brain tumor, but they can be troublesome.
Sometimes a large area of dead cells, called radiation necrosis, forms at the site of the radiation in
the brain. This can happen months to years after radiation is given, and can cause symptoms like
seizures, mental status changes, headaches, trouble speaking or walking, and other changes. It can
be hard to tell if these symptoms are from necrosis or from the tumor coming back. Imaging tests
like MRI or PET scans can help, but biopsy may be needed to be sure. Patients with radiation
necrosis usually do better than patients whose brain tumors come back. But still, a number of
patients with radiation necrosis do poorly or even die.
Lung
When radiation treatments include the chest, it can affect the lungs. One early change is a decrease
in the levels of a substance called surfactant, which helps keep the air passages open. Low
surfactant levels keep the lungs from fully expanding. This may cause shortness of breath or a
cough. These symptoms are sometimes treated with steroids. Depending on the location of the area
getting radiation, some people also have trouble swallowing.
Radiation pneumonitis occurs in about 5 to 20% of people get radiation therapy for lung cancer. It
can also be caused by radiation to the chest for breast cancer, lymphomas, or other cancers. This
inflammation may occur from about 6 weeks to 6 months after completing external radiation
therapy. Common symptoms include shortness of breath, chest pain, cough, and fever. Radiation
pneumonitis is treated by trying to decrease the inflammation. Steroids, like prednisone, are
usually used.
Another possible effect radiation can have on the lungs is fibrosis (stiffening or scarring). This
means the lungs are less able to expand and take in air. Fibrosis can cause shortness of breath and
make it hard to exercise. This problem may show up months or even years after treatment.
Digestive tract
Radiation to the chest and abdomen (belly) may cause swelling and inflammation in the esophagus
(the tube connecting the throat to the stomach), stomach, or intestine (bowels). This can cause
pain, nausea, vomiting, or diarrhea. Antacids, sometimes combined with a numbing medicine such
as lidocaine, may help relieve pain from an inflamed esophagus. Nausea and vomiting can also be
treated with medicines. If it’s severe, some patients may need intravenous (IV) fluids to avoid or
treat dehydration and strong medicines like morphine to treat pain. Diarrhea also can be treated
with medicines and may be helped by avoiding spicy, fried, or high fiber foods.
Digestive problems usually go away within a week or 2 of the last radiation treatment. Rarely they
can be serious enough to cause long-term problems – such as scarring that can cause permanent
narrowing of the esophagus, or ulcers that can cause abnormal openings in the intestine. Diarrhea
and bleeding can result if the colon or rectum is affected (colitis or proctitis).
Reproductive/sex organs
Fertility in men: Radiation to the testicles can cause permanent loss of sperm production. Unless
the cancer is in the testicles, they can usually be protected from radiation by using a shield called a
clam shell.
See our document called Fertility and Men With Cancer to learn more about preserving fertility in
men.
Fertility in women: It’s harder to protect the ovaries when women are getting radiation to the
abdomen (belly). If both ovaries are exposed to radiation, early menopause and permanent
infertility can result. Sparing one ovary can prevent these side effects. If the uterus (womb) is
exposed, radiation can cause scarring and fibrosis.
See our document called Fertility and Women With Cancer to learn more about preserving fertility
in women.
Sexual effects of radiation therapy on women: Radiation to the pelvic area can make the vagina
tender and inflamed during and for a few weeks after treatment. The area may scar as it heals. This
scarring can interfere with the vagina’s ability to stretch. The lining of the vagina also gets thinner,
and might bleed slightly after sex. A few women get ulcers, or sore spots, in their vaginas. It may
take many months for these areas to heal after radiation therapy ends.
The scarring that normally occurs after pelvic radiation can also shorten or narrow the vagina so
much that a woman might not be able to have sex or get a Pap smear without pain. This can often
be prevented by stretching the walls of the vagina a few times a week. One way to do this is to
have sex that includes vaginal penetration at least 3 to 4 times a week. Another option is to use a
vaginal dilator. A dilator is a plastic or rubber rod or tube used to stretch out the vagina. It feels
much like putting in a large tampon for a few minutes. Even if a woman is not interested in staying
sexually active, it helps allow her doctor to do pelvic exams. This is an important part of follow-up
care after treatment. Doctors, nurses, and other health care team members can tell you more.
As long as a woman is not bleeding heavily from a tumor in her bladder, rectum, uterus, cervix, or
vagina, she may be able to have sex during pelvic radiation therapy. The outer genitals and vagina
are just as sensitive as usual. But if any of these areas are being radiated, sex may be
uncomfortable because of sore spots or inflamed tissues in the vulva or vagina. Other side effects
of radiation can also make a person less interested in sex during treatment. Women should discuss
these issues with their doctors. If you have sexual problems during or after radiation, talk with
your doctor or nurse. You can read more about this in our booklet, Sexuality for the Woman With
Cancer.
Sexual impact of radiation therapy on men: Radiation therapy to the pelvis can damage the
arteries and nerves that supply the penis and as a result, cause problems with erections. The higher
the dose of radiation and the wider the area of the pelvis treated, the greater the chance that a man
will develop erection problems.
About 1 man in 3 who gets radiation in the pelvic area will notice a change in his ability to have
erections. This change most often develops slowly over the first couple of years after radiation
treatment. Some men continue to have full erections but lose them before reaching climax. Others
no longer get firm erections at all. Men who are older, who didn’t have full erections before they
were treated, who have high blood pressure, or who have been heavy smokers seem to have a
higher risk of having erection problems after radiation.
Testosterone is a male hormone that plays an important role in erections. Some men have less
testosterone after pelvic radiation. The testicles, which make testosterone, may be affected either
by a mild dose of scattered radiation or by the general stress of cancer treatment. Testosterone
levels usually return to normal within 6 months of radiation therapy. But if a man has problems
with low sexual desire after cancer treatment, the doctor may decide to do a blood test to find out if
testosterone is low. Some men can take testosterone to raise low levels to normal. Men with
prostate cancer should know that replacement testosterone can speed up the growth of prostate
cancer cells. You can read more about sexual problems during cancer in our booklet called
Sexuality for the Man With Cancer.
Second cancers
The link between radiation and cancer was confirmed many years ago through studies of the
survivors of the atomic bombs in Japan, the exposures of workers in certain jobs, and patients
treated with radiation therapy for cancer and other diseases.
Some cases of leukemia are related to past radiation exposure. Most develop within a few years of
exposure, with the risk peaking at 5 to 9 years, and then slowly declining. Other types of cancer
that develop after radiation exposure have been found to take much longer to show up. These are
solid tumor cancers, like cancer of the breast or lung. Most are not seen for at least 10 years after
radiation exposure, and some are diagnosed even more than 15 years later.
Radiation therapy techniques have steadily improved over the last few decades. Treatments now
target the cancers more precisely, and more is known about setting radiation doses. These
advances are expected to reduce the number of secondary cancers that result from radiation
therapy. Overall, the risk of second cancers is low and must be weighed against the benefits gained
with radiation treatments.
To learn more about this, please see our document called Second Cancers Caused by Cancer
Treatment.
Other general health concerns
Many patients want to know how they can improve their general health to help their body’s natural
defenses fight the cancer. They may also want to do things to speed up their recovery from
radiation’s side effects.
Quitting smoking
For patients who still smoke, it’s never too late to quit. Studies show that people with some types
of cancer who keep smoking during and after treatment have a greater risk of the cancer coming
back and of new cancers forming. Smoking can increase many side effects, too. It can also reduce
appetite at a time when extra nutrition is needed. For help quitting smoking, please see our Guide
to Quitting Smoking or call us at 1-800-227-2345.
Diet
You may need to avoid certain foods because of your treatment, but eating a balanced diet is
important. It’s also important to take in enough calories to provide energy for healing. If you’re
having trouble getting enough nutrition or are worried about what types of food you should be
eating, ask your doctor about a referral to a dietitian. You may also want to see our document
called Nutrition for the Person With Cancer During Treatment: A Guide for Patients and Families.
Patients should check with their doctors before taking any vitamins or supplements on their own
during radiation treatment. Certain vitamins, such as A, E, and C act as antioxidants. They help
keep ions (electrically charged particles) that damage DNA in cells from forming. This damage is
thought to have an important role in causing cancer. There is some evidence that getting enough
antioxidants might help reduce the risk of getting some types of cancer. But during treatment,
radiation therapy works to fight cancer by producing these ions, which severely damage the DNA
of cancer cells. Some scientists believe that taking high doses of antioxidants, including certain
vitamin and mineral supplements, during treatment may make radiation therapy less effective by
reducing this particular way of damaging cancer cells. So far, studies have not fully tested this
theory. While this is being researched, many radiation oncologists recommend the following:
• If your doctor has not prescribed vitamins for a specific reason, it’s best not to take any on your
own.
• A single multivitamin tablet each day is probably OK for patients who want to take a vitamin
supplement, but check with your doctor first.
• It’s safest to avoid taking high doses of antioxidant vitamins or other antioxidant supplements
during treatment. Ask your doctors when it might be safe to start such vitamins or supplements
after treatment is finished.
What’s new in radiation therapy?

New ways of delivering radiation therapy are making it safer and more effective. Some of these
methods are already being used, while others need more study before they can be approved for
widespread use. And scientists around the world continue to look for better and different ways to
use radiation to treat cancer. Here are just a few areas of current research interest:
Hyperthermia is the use of heat to treat cancer. Heat has been found to kill cancer cells, but when
used alone it does not destroy enough cells to cure the cancer. Heat created by microwaves and
ultrasound is being studied in combination with radiation and appears to improve the effect of the
radiation. For more information, see our document called Hyperthermia to Treat Cancer.
Hyperbaric oxygen therapy consists of breathing pure oxygen while in a sealed chamber that has
been pressurized at 1½ to 3 times normal atmospheric pressure. It helps to increase the sensitivity
of certain cancer types to radiation. It’s also being tested to see if it can reverse some of the
damage to normal body tissues caused by radiation.
Radiosensitizers are a growing field in cancer treatment. Researchers are continuing to look for
new substances that will make tumors more sensitive to radiation without affecting normal tissues.
Radioprotectors are substances that protect normal cells from radiation. These types of drugs are
useful in areas where it’s hard not to expose vital normal tissues to radiation when treating a
tumor, such as the head and neck area. Some radioprotectors, such as amifostine (Ethyol®), are
already in use, while others are being studied in clinical trials.
To learn more
More information from your American Cancer Society
Here is more information you might find helpful. You also can order free copies of our documents
from our toll-free number, 1-800-227-2345, or read them on our Web site, www.cancer.org.
Living with cancer

After Diagnosis: A Guide for Patients and Families (also in Spanish)
Coping With Cancer in Everyday Life (also in Spanish)
Distress in People with Cancer
Nutrition for the Person With Cancer During Treatment: A Guide for Patients and Families (also in
Spanish)
Helping Children When a Family Member Has Cancer: Dealing With Treatment (also in Spanish)
Sexuality for the Man With Cancer (also in Spanish)
Sexuality for the Woman With Cancer (also in Spanish)
Cancer treatment
Understanding Radiation Therapy: A Guide for Patients and Families (also in Spanish)
Understanding Chemotherapy: A Guide for Patients and Families (also in Spanish)
Understanding Cancer Surgery: A Guide for Patients and Families (also in Spanish)
Clinical Trials: What You Need to Know
Hyperthermia
Choosing a Doctor and a Hospital (also in Spanish)
Health Professionals Associated With Cancer Care
Side effects of cancer treatment

Fatigue in People With Cancer
Nausea and Vomiting
Fertility and Cancer: What Are my Options? (also in Spanish)
Second Cancers Caused by Cancer Treatment
For caregivers of people with cancer

What it Takes to Be a Caregiver
Caring for the Patient With Cancer at Home: A Guide for Patients and Families (also in Spanish)
Quitting smoking
Guide to Quitting Smoking (also in Spanish)
National organizations and Web sites*

Along with the American Cancer Society, other sources of information and support include:
American Society for Radiation Oncology (ASTRO)
Toll-free number: 1-800-962-7876
Website: www.astro.org
Website for patients: www.rtanswers.org
Patient website has a locator of member radiation oncologists. Free brochures, including
specific brochures on radiation for bladder, breast, colorectal, gynecologic, head and neck,
Hodgkin’s, lung, non-Hodgkin’s, skin, and prostate cancers are available.
National Cancer Institute
Toll-free number: 1-800-4-CANCER (1-800-422-6237)
Web site: www.cancer.gov
Web site in Spanish: www.cancer.gov/espanol
Offers accurate, up-to-date information about cancer to patients, their families, and the
general public.
*Inclusion on this list does not imply endorsement by the American Cancer Society.
No matter who you are, we can help. Contact us anytime, day or night, for cancer-related
information and support. Call us at 1-800-227-2345 or visit www.cancer.org.
References
American Society for Therapeutic Radiology and Oncology. Answers to Your Radiation Therapy
Questions. Accessed at www.rtanswers.org on October 18, 2013.
Brown AP, Chen J, Hitchcock YJ, et al. The risk of second primary malignancies up to three
decades after the treatment of differentiated thyroid cancer. J Clin Endocrinol Metab.
2008;93(2):504-515.
Constine LS, Milano MT, Friedman D, et al. Late Effects of Cancer treatment on Normal Tissues.
In: Halperin EC, Perez CA, Brady LW, (Eds.) Perez and Brady’s Principles and Practice of
Radiation Oncology, 5th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2008: 320-355.
Douglas JG, Goodkin R, Laramore GE. Gamma knife stereotactic radiosurgery for salivary gland
neoplasms with base of skull invasion following neutron radiotherapy. Head Neck.
2008;30(4):492-496.
Fisher DR. Medical Isotope Production and Use (National Isotope Development Center). 2009.
Accessed at www.isotopes.gov/outreach/reports/Medical_Isotope_Production_Use.pdf on October
1, 2013.
Gosselin-Acomb TK. Principles of Radiation Therapy. In: Henke Yarbro C, Hansen Frogge M,
Goodman M, eds. Cancer Nursing Principles and Practice. 6th ed. Boston: Jones and Bartlett
Publishers, Inc. 2005:229-249.
Halperin EC. Particle therapy and treatment of cancer. Lancet Oncol. 2006;7:676-685.
Halperin EC, Perez CA, Brady LW (eds). Principles and Practice of Radiation Oncology, Fifth
Ed. Philadelphia, Pa: Lippincott Williams & Wilkins 2008.
Hede K. Research groups promoting proton therapy “lite.” JNCI. 2006;98:1682-1684.
International Atomic Energy Agency, Radiation Protection of Patients. Radiation Protection in
Radionuclide therapy. Accessed at
http://rpop.iaea.org/RPOP/RPoP/Content/Documents/TrainingNuclearMedicine/Lectures/RPNM_
Part08_therapy_WEB.ppt on October 18, 2013.
Jongen Y. Radiotherapy systems using proton and carbon beams. Bull Mem Acad R Med Belg.
2008;163(10-12):471-8; discussion 479-80.
Khan FM. The Physics of Radiation Therapy. 4th ed. Philadelphia, Pa: Lippincott Williams &
Wilkins 2010.
Kry SF, Salehpour M, Followill DS, et al. The calculated risk of fatal secondary malignancies from
intensity-modulated radiation therapy. Int J Radiat Oncol Biol Phys. 2005;62(4):1195-1203.
Morgan MA, Haken RKT, Lawrence TS. Radiation Oncology. In: DeVita VT Jr, Lawrence TS,
Rosenberg SA (Eds.) DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of
Oncology, 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2011: 289-311.
National Cancer Institute. Radiation Therapy and You: Support for People with Cancer. Accessed
at www.cancer.gov/cancertopics/radiation-therapy-and-you on October 1, 2013.
National Cancer Institute. Radiation Therapy for Cancer FactSheet. Accessed at
www.cancer.gov/cancertopics/factsheet/Therapy/radiation on October 1, 2013.
Paes FM, Serafini AN. Systemic Metabolic Radiopharmaceutical Therapy in the Treatment of
Metastatic Bone Pain. Semin Nucl Med. 2010;40:89-104.
Reed SI. Cell Cycle. In: DeVita VT Jr, Lawrence TS, Rosenberg SA (Eds.) DeVita, Hellman, and
Rosenberg’s Cancer: Principles and Practice of Oncology, 9th ed. Philadelphia, Pa: Lippincott
Williams & Wilkins; 2011: 68–81.
Sawka AM, Lakra DC, Lea J, et al. A systematic review examining the effects of therapeutic
radioactive iodine on ovarian function and future pregnancy in female thyroid cancer survivors.
Clin Endocrinol (Oxf). 2008;69(3):479-490.
Schneck MJ. Radiation Necrosis, Jan 2013. Medscape. Accessed at
http://emedicine.medscape.com/article/1157533-overview on October 13, 2013.
Sheets NC, Goldin GH, Meyer AM, et al. Intensity-modulated radiation therapy, proton therapy, or
conformal radiation therapy and morbidity and disease control in localized prostate cancer. JAMA.
2012;307(15):1611–1620.
Last Medical Review: 10/23/2013
Last Revised: 10/23/2013
2013 Copyright American Cancer Society

Lecture ‐4‐
Bioradiation
1-Radiation Response on the Tissue Level
The appearance of radiation damage is related with two factors:
1-The biologic stress on the cell .
2-The conditions to which the cell is exposed pre and post irradiation
The time required for the tissue to respond to radiation damage can be predicted
on the basis of the cell cycle kinetics of these critical cells, and there are three
Biologic Factors moderating Cell injury by irradiation:
1- Cell cycle.
2- Intracellular repair.
3- Hypoxia.
2-Normal Tissue Response to Radiation
Normal tissue response to radiation classified on the time taken to exhibit clinical
injury
1-Acute responding tissues: express injury during or within 2 - 3 weeks of the

completion of radiotherapy e.g., skin, oral mucosa
2-Late responding tissues: express injury several months to years after

irradiation e.g., kidney, lung, CNS
1
Lecture ‐4‐
Bioradiation
3-Biological Effects of Ion Irradiation
The biological effects depend on dose, ion type, LET, and the influence of the
cell type .All effects will be discussed with respect to the particular physical
characteristics of ion beams, i.e., track structure. Also environmental factors
play vital role in Biological effects of ion irradiation. For Biological effect of
Radiation the following Aspect should be take into account:
3-1 The Relative of Biological Effectiveness (RBE):
3-2 Systematic of RBE which includes:
3-2-1 Dose Dependence
3-2-2 Energy/LET Dependence
The increased RBE is not unique for all different kinds of charged particle
radiation. Instead, it strongly depends on the particular physical characteristics
of the ion beam .
3-2-3 Particle Dependence
3-2-4 Cell Type Dependence
These genetic differences lead to correspondingly different radio sensitivities

after X-irradiation.
3-3- The Role of Increased Ionization Density
Increased ionization density was assumed to lead to more complex and thus less
reparable damage.
3-3-1 Double Strand Break of DNA Induction and Rejoining
The increased ionization density to lead to a higher
Yield of severe damage, e.g., DSB (Double Strand Break)
2
Lecture ‐4‐
Bioradiation
3-3-2 Chromosome Aberrations
Investigation of chromosome aberrations also revealed the influence of radiation
quality on the rate of rejoining and repair of DSB., and leading also to the higher
rate of exchange type aberrations between different chromosomes
3-4 Fractionated Irradiation
At least part of the damage can be repaired, leading to an overall decreased effect
of fractionated compared to single dose exposure.
3- 5 Bystander Effects
The ‘bystander effect’ is used to describe situations where not only the primarily
damaged cells respond to radiation, but also neighboring cells show a response
without being directly damaged. The bystander effect could also
explain at least partially the hypersensitivity observed after irradiation with
charged particle beams at very low doses.
Figure 1:Bystander Effect
3
Lecture ‐4‐
Bioradiation
3-6 Tissue Effects
Cells in a tissue are usually connected by complex communication networks. In

fact there are first indications that bystander effects cannot only be detected in in
vitro systems, but also in in vivo-like systems such as, e.g., tissue explants Since
bystander effects play a role at low doses and low influences, they might be in
particular relevant for studies of mutation and transformation related to
radiation protection .(Figure 2)
Figure 2: Mechanism of radiation effect on Tissue
4
Lecture ‐4‐
Bioradiation
4-Models of Biological Action of Radiation
Modeling plays an important role for the mechanistic understanding of radiation

action as well as for practical applications in radiation protection and
radiotherapy.
4-1 Dual Radiation Action
Based on the analysis of chromosome aberrations, the first models specifically

based on lesion interaction. Estimates revealed that interaction should take place
over distances of typically micrometers, so that the distribution of damage on a
micrometer scale was thought to be of particular importance. Since the spatial
distribution of damage cannot be investigated directly, the spatial distribution of
energy deposition was taken as a measure reflecting the damage distribution.
Among others, this is a theory of dual radiation action (TDRA).
4-2 Cluster Models
Clusters of damage should then result from clusters of energy deposition, and
thus several models have been developed which are particularly based on
detailed investigations of cluster properties of high-LET radiation with
nanometer resolution.
4-3 Irregular Track Structure Models
Another class of models called ‘amorphous track structure’ models. The two key
features of these models are:
5
Lecture ‐4‐
Bioradiation
A-They make use of the particular features of track structure in a certain
simplified.
B- They are based on the assumption that no principle difference between the
biological actions of low- and high-LET radiation exists, because in both cases
the biological effect is due to the action of the secondary electrons. homogenous
distribution of sensitivity throughout the nucleus is assumed as a first
approximation.
Figure 3: Direct and Indirect effect of Radiation.

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Reactor Concepts Manual Biological Effects of Radiation

Whether the source of radiation is

USNRC Technical Training Center 9-1 0603

Radiation Causes Ionizations of:

THE WHOLE BODY

USNRC Technical Training Center 9-2 0603

USNRC Technical Training Center 9-3 0603

USNRC Technical Training Center 9-4 0603

Radiolytic Decomposition of Water in a Cell

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Cellular Sensitivity to Radiation

Lymphocytes and Blood Forming Cells

Reproductive and Gastrointestinal (GI) Cells

Nerve and Muscle Cells

USNRC Technical Training Center 9-6 0603

NORMAL REPAIR OF DAMAGE CELL DIES FROM DAMAGE

USNRC Technical Training Center 9-7 0603

Blood Forming Organs

Reproductive and Gastrointestinal Tract Organs

Muscle and Brain

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USNRC Technical Training Center 9-9 0603

Whole Body Sensitivity Factors

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Low Doses (Chronic)

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Occupation High Dose Exposures

Non-Occupational High Dose Exposures

An example of a nonoccupational accident occurred in 1987 in Goiania, Brazil. An abandoned medical

A recent inadvertent criticality event occurred in a fuel processing plant in Japan.

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High Dose Effects

Dose (Rad) Effect Observed

15 - 25 Blood count changes in a group of people

50 Blood count changes in an individual

100 Vomiting (threshold)

150 Death (threshold)

320 - 360 LD 50/60 with minimal care

480 - 540 LD 50/60 with supportive medical care

1,100 LD 50/60 with intensive medical care (bone marrow

USNRC Technical Training Center 9-13 0603

Other High Dose Effects

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Acute Radiation Syndrome (ARS)

Syndrome Organs Affected Sensitivity

Hematopoietic Blood forming organs Most sensitive

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Summary of Biological Response to High Doses of Radiation

< 5 rad - No immediate observable effects

~ 5 rad to 50 rad - Slight blood changes may be detected by medical evaluations

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Annual Exposure to Average U.S. Citizen

Approximate Total 360

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Categories of Effects of Exposure to

Genetic - The effect is suffered by the offspring of the individual exposed.

In-Utero - Some mistakenly consider this to be a genetic consequence of radiation exposure,

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Lung cancer - uranium miners