Sodium Benzoat
Sodium Benzoat
Sodium Benzoat
a r t i c l e i n f o a b s t r a c t
Article history: In this study, the genotoxic effects of sodium benzoate (SB) and potassium benzoate (PB) were investi-
Received 12 August 2010 gated in cultured human peripheral lymphocytes using chromosomal aberrations (CA), sister chromatid
Accepted 29 November 2010 exchange (SCE), and micronuclei (MN). The level of nuclear DNA damage of SB and PB were also evaluated
Available online 3 December 2010
using the comet assay. The lymphocytes were incubated with different concentrations of SB (6.25, 12.5,
25, 50, and 100 lg/ml) and PB (62.5, 125, 250, 500, and 1000 lg/ml). A significant increase was observed
Keywords: in CA, SCE, and MN, in almost all treatments compared to negative controls. SB and PB significantly
Genotoxicity
decreased the mitotic index (MI) in all the treatments, compared to the negative controls. However, nei-
Food additive
Sodium benzoate
ther of the additives affected the replication index (RI). Although SB significantly increased DNA damage,
Potassium benzoate PB did not cause a significant increase in DNA damage. The present results indicate that SB and PB are
Human lymphocytes clastogenic, mutagenic and cytotoxic to human lymphocytes in vitro.
Ó 2010 Elsevier Ltd. All rights reserved.
0278-6915/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.fct.2010.11.040
764 N. Zengin et al. / Food and Chemical Toxicology 49 (2011) 763–769
activity in S. typhimurium strains. Vernole et al. (1987) studied the for determination of the replication index (RI). The RI was calculated according to
the following formula; (1 M1) + (2 M2) + (3 M3)/N (N = number of observed
cytogenetic effects of 1-p-(3-methyltriazeno) benzoic acid potas-
cells) where M1, M2, and M3 represented the number of cells undergoing the first,
sium salts in human lymphocytes. They reported that this chemical second, and third mitosis, respectively (Schneider et al., 1981).
caused a dose-dependent increase in the frequency of chromo- Micronuclei preparation was performed according to the procedures of Fenech
somal breaks. Vernole et al. (1988) also reported the clastogenic (2000) and Palus et al. (2003). The human lymphocyte cultures were incubated at
potential of 1-p-(3-methyltriazeno) benzoic acid potassium salts 37 °C for 72 h and treated with five different concentrations of SB and PB during
the last 48 h. Forty-four hours after the start of the culture, cytochalasin B (Cyt-B)
via sister-chromatid exchange in human lymphocytes.
was added at a final concentration of 5.2 lg/mL, to arrest cytokinesis. SB and PB
To evaluate the genotoxic effects induced by physical and did not alter the pH of the culture medium. Micronuclei were scored from 1000
chemical agents, various test systems have been described in bac- binucleated cells (BN) per donor (totally 2000 binucleated cells per concentration).
teria, in mammalian cells, and in plants (Prival et al., 1991; Mac- Cell proliferation was evaluated using the cytokinesis-block proliferation index
(CBPI), which indicated the average number of cell cycles a given cell had under-
ioszek and Kononowicz, 2004; Yılmaz et al., 2008a; Arslan et al.,
gone (Scarfi et al., 1997). Five hundred lymphocytes were scored from per donor
2008; Mamur et al., 2010). Some of these test systems that are (totally 1000 lymphocytes) to evaluate the percentage of cells with 1–4 nuclei. CBPI
widely used are chromosomal aberrations (CAs), sister-chromatid was calculated according to Surrales et al. (1995), as follows; (1 N1) + (2 N2) +
exchanges (SCEs), and micronuclei (MN) tests in cultured human (3 (N3 + N4)/N, where N1–N4 represent the number of cells with 1–4 nuclei,
peripheral lymphocytes, and recently the comet assay, in isolated respectively, and N is the total number of cells scored. MN were accepted only when
(i) they were separated from the main nuclei, but included within the correspond-
lymphocytes (Rencüzoğulları et al., 2001; Macioszek and Kon-
ing cytoplasm, (ii) they had a chromatin material similar to that of the main nuclei,
onowicz, 2004; Yüzbasßıoğlu et al., 2006; Yılmaz et al., 2008b; Ma- (iii) they were coplanar to the main nuclei (Çelik, 2006).
mur et al., 2010). Primary DNA damaging effects caused by the SB and PB were determined using
The purpose of this study was to evaluate the potential geno- the comet assay according to Singh et al.’s (1988) method, with some modifications.
The methods followed for the comet assay in human lymphocytes was given in de-
toxic effects of food preservatives SB and PB, using in vitro CA,
tail in the study of Mamur et al. (2010). The lymphocytes were isolated using the
SCE, and MN tests on human peripheral lymphocytes and the co- Biocoll separating solution. To detect the viability of cells, the trypan blue exclusion
met assay on isolated human lymphocytes. With the great increase test was used. Cell viability was >98%. Isolated human lymphocytes were incubated
in the use of food additives this study obtained more data about with concentrations of SB (6.25, 12.5, 25, 50, and 100 lg/mL) and PB (62.5, 125, 250,
screening the potential effects. 500, and 1000 lg/mL) for 1 h at 37 °C. Negative and positive controls (100 mM
H2O2, 0.30 lg/mL) were also included. To detect DNA damaging capacity of the
SB and PB, DNA was electrophoresed at 25 V, 300 mA for 20 min.
2. Materials and methods Image analysis and comet scoring were examined using the fluorescent micro-
scope (Olympus BX51) equipped with an excitation filter of 546 nm and a barrier
In the current study, human peripheral lymphocytes were used as the test sys- filter of 590 nm, at 400 magnification. A slide was prepared for each dose of SB
tem. The test substance SB (Cas. No: 532-32-1) was obtained from Merck and PB and PB. The tail moment (%) of 100 comets on the slide (totally 200 comets per con-
(Cas. No: 582-25-2) was obtained from Emerald. The chemical structure, molecular centration) were determined using a specialized image analyzes system (Comet As-
formula and molecular weight of SB and PB are shown in Fig. 1. These chemicals say IV, Perceptive Instruments Ltd., UK).
were dissolved in distilled water. The other chemicals cytochalasin-B (Cas. No: For the statistical analysis of the results, the z-test was applied for the percent-
14930-96-2), mitomycin C (Cas. No: 50-07-7), bromodeoxyuridine (Cas. No: 59- age of abnormal cells with CA, CA/cell, RI, CBPI, MI, MN, and the t-test for SCEs and
14-3), NaCl (Cas. No: 7647-14-5), colchicine (Cas. No: 64-86-8) were obtained from the comet assay. Dose–response relationships were determined from the correla-
Sigma. DMSO (Cas. No: 67-68-5), NaOH (Cas. No: 1310-73-2), Tris (Cas. No: 77-86- tion and regression coefficients for the percentage of abnormal cells, CA/cell, SCE,
1), EDTA (Cas. No: 6381-92-6), Triton X-100 (Cas. No: 9002-93-1), Low Melting Aga- MN, and the mean comet tail moment.
rose (Cas. No: 9012-36-6), Normal Melting Agarose (Cas. No: 9012-36-6), EtBr (Cas.
No: 1239-45-8), H2O2 (Cas. No: 7722-84-1) were obtained from Applichem.
3. Results
The study was carried out using blood samples from two healthy donors (non-
smokers, of age 25 years), with no medication for at least 3 weeks prior, and not
having had a radiological examination within the prior 3 months. 3.1. Chromosomal aberrations assay
For the SCE and CA studies, whole blood 0.2 ml was added to 2.5 ml chromo-
some medium B (containing fetal bovine serum, heparin, antibiotics, phytohemag- Sodium benzoate and PB induced a significant increase in the
glutinin) supplemented with 10 lg/mL bromodeoxyuridine. The cultures were
incubated at 37 °C for 72 h. SB and PB did not change the pH of the culture medium.
frequency of CAs and CA/cell in all concentrations and treatment
Human lymphocytes were treated with different concentrations of SB (6.25, 12.5, periods as compared to the negative control (Table 1). These in-
25, 50, and 100 lg/mL) and PB (62.5, 125, 250, 500, and 1000 lg/mL) for 24 and creases in the frequency of CAs and CA/cell were dose-dependent,
48 h. In addition, negative and positive controls (mitomycin-C = MMC, 0.20 lg/ both in the 24- and 48-h treatments (for SB, r = 0.99 and 0.97 and
mL) were also maintained in all experiments. The methods of Evans (1984) and
for PB, r = 0.97 and 0.97 at 24- and 48-h, respectively). Both the
Perry and Thompson (1984) were followed in the preparation of CA and SCE tests
with minor modifications (Yüzbasßıoğlu et al., 2006). Chromosomal abnormalities additives caused six types of structural aberrations (chromatid
were scored from 100 well-spread metaphases per donor (totally 200 metaphases and chromosome breaks, chromatid exchanges, fragments, sister-
per dose level). The mitotic index (MI) was determined by scoring 1000 cells from chromatid unions, and dicentric chromosomes) and a numerical
each donor. aberration (polyploidy). Chromatid (SB = 73.98%; PB = 58.64%)
For the SCE assay, the slides were stained with Giemsa, according to Speit and
Houpter’s (1985) method, with some modifications (Mamur et al., 2010). The num-
and chromosome breaks (SB = 16.47%; PB = 29.51%) were the most
ber of SCEs (25 cells from each donor, a total of 50 cells per concentration) under the frequent aberrations in all the experimental groups.
second metaphases was scored. In addition, 100 cells from each donor were scored
3.2. Sister-chromatid exchanges, cell cycle and mitotic index
Table 1
Chromosome aberrations in cultured human lymphocytes treated with sodium benzoate and potassium benzoate.
ctb: Chromatid break, csb: chromosome break, cte: chromatid exchange, f: fragment, scu: sister chromatid union, dic: dicentric chromosome, p: polyploidy.
Totally 200 cells were scored for each treatments.
MMC: mitomycin-C.
*
Significant from the control P < 0.05 (z test).
**
Significant from the control P < 0.01 (z test).
***
Significant from the control P < 0.001 (z test).
increased at 25, 50, and 100 lg/mL concentrations of SB and 125, 4. Discussion
250, 500, and 1000 lg/mL concentrations of PB. These increases
were dose-dependent (SB r = 0.97, PB r = 0.91). In this study, the genotoxic potential of SB and PB was investi-
gated, with chromosomal aberrations, sister-chromatid exchanges
3.4. Mitotic, replication and nuclear division indices and micronucleus analysis in cultured human peripheral lympho-
cytes, as well as, single cell gel electrophoresis (SCGE) or ‘comet as-
Sodium benzoate significantly decreased the frequency of the say’ in isolated lymphocytes, which are used as the most rapid,
mitotic index at concentrations of 12.5, 25, 50, and 100 lg/mL at sensitive, and useful assays and have been proved to be good indi-
the 24-h treatment and all concentrations at the 48-h treatment. cators of DNA damage (Macioszek and Kononowicz, 2004; Mpoun-
The other additive PB significantly decreased the frequency of toukas et al., 2008; Mamur et al., 2010). In vitro genotoxicity tests
the mitotic index at concentrations of 250, 500, and 1000 lg/mL detected compounds that induced genetic damage, directly or indi-
at the 24-h treatment and all concentrations at the 48-h treatment. rectly, by different mechanisms. They are considered to be the
Significant concentration response correlations were observed in markers of early biological effects of carcinogen exposure (Liou
the MI at both treatment periods (for SB r = 0.97, 0.89, for PB et al., 2002). In all these test systems, data showed that both addi-
r = 0.93, 0.95 at 24 and 48 h, respectively) (Table 4). On the tives induced genotoxicity at almost all concentrations and treat-
other hand neither had an additive effect in RI, compared to the ment times and also decreased the mitotic index.
negative controls (Table 4). The CBPI value was not affected by Both food additives significantly increased the frequency of CAs
the treatments of these additives. and CA/cell in all treatments groups when compared with their
negative controls. These additives induced seven types of chromo-
3.5. Comet assay somal aberrations, which indicated their clastogenic effects. In this
study chromatid and chromosome breaks had been observed as the
According to the comet assay results, the comet tail moment most common aberrations. Chromosomal breakage could result in
significantly increased in all the concentrations of sodium benzo- a number of different structural rearrangements, some of which
ate, but this increase was not concentration-dependent. On the gave rise to abnormalities of chromosomal segregation at mitosis
other hand, potassium benzoate did not significantly increase the (Gisselsson, 2001). Increased levels of CA have been associated
comet tail moment in any concentration (Table 5). with increased cancer risk (Hagmar et al., 1994).
766 N. Zengin et al. / Food and Chemical Toxicology 49 (2011) 763–769
Table 4
Frequency of the replication, mitotic and cytokinesis-block proliferation indices in cultured human lymphocytes treated with sodium benzoate and potassium benzoate.
studies. All food additives must be kept under continuous observa- Inoue, A., Yokomori, K., Tanabe, H., Mizusawa, H., Sofuni, T., Hayashi, Y., Tsuchida, Y.,
Shimatake, H., 1997. Extensive genetic heterogeneity in the neuroblastoma cell
tion and must be re-evaluated whenever necessary, in the light of
line NB(TU)1. International Journal of Cancer 72, 1070–1077.
changing conditions of use and new scientific information (Council Ishidate, M., Sofuni Jr., T., Yoshikawa, K., Hayashi, M., Nohmi, T., Sawada, M.,
directive 89/107/EEC). Further studies on the genotoxic properties Matsuoka, A., 1984. Primary mutagenicity screening of food additives currently
of sodium benzoate and potassium benzoate, with the help of other used in Japan. Food and Chemical Toxicology 22, 623–636.
Jain, A.K., Andsorbhoy, R.K., 1988. Cytogenetical studies on the effects of some
tests for genotoxicity, should be conducted. chlorinated pesticides. III. Concluding remarks. Cytologia 53, 427–436.
Liou, S.H., Chen, Y.H., Loh, C.H., Yang, T., Wu, T.N., Chen, C.J., Hsieh, L.L., 2002. The
association between frequencies of mitomycin C-induced sister-chromatid
Conflict of Interest exchange and cancer risk in arseniasis. Toxicology Letters 129, 237–243.
Macioszek, V.K., Kononowicz, A.K., 2004. The evaluation of the genotoxicity of two
The authors declare that there are no conflicts of interest. commonly used food colors: quinoline yellow (E 104) and Brilliant black BN (E
151). Cellular and Molecular Biology Letters 9, 107–122.
Mamur, S., Yüzbasßıoğlu, D., Ünal, F., Yılmaz, S., 2010. Does potassium sorbate induce
Acknowledgement genotoxic or mutagenic effects in lymphocytes? Toxicology In Vitro 24, 790–794.
Michaelsson, G., Juhlin, L., 1973. Urticaria induced by preservatives and dye
additives in foods and drugs. British Journal Dermatology 88, 525–532.
This study was partially supported by Gazi University Research Miller, M., Millstone, E., 1987. Food Additives Campaign Team: Report on Colour
Fund under Project No. 05/2008-54. Additives. FACT, 25 Horsell Road, London N5 1XL.
Mpountoukas, P., Vantarakis, A., Sivridis, E., Lialiaris, T., 2008. Cytogenetic study in
cultured human lymphocytes treated with three commonly used preservatives.
References Food and Chemical Toxicology 46, 2390–2393.
Njagi, G.D., Gopalan, H.N., 1982. Cytogenetic effects of the food preservatives
Abe, S., Sasaki, M., 1977. Chromosome aberrations and sister-chromatid exchanges sodium benzoate and sodium sulphite on Vicia faba root meristems. Mutation
in Chinese Hamster cells exposed to various chemicals. Journal of the National Research 102, 213–219.
Cancer Institute 58, 1635–1641. Palus, J., Rydzynski, K., Dziubaltowska, E., Wyszynska, K., Natarajan, A.T., Nilsson, R.,
Albertini, R.J., Anderson, D., Douglas, G.R., Hagmar, L., Hemminki, K., Merlo, F., 2003. Genotoxic effects of occupational exposure to lead and cadmium.
Natarajan, A.T., Norppa, H., Shuker, D.E.G., Tice, R., Waters, M.D., Aitio, A., 2000. Mutation Research 540, 19–28.
IPCS guidelines for the monitoring of genotoxic effects of carcinogens in Perry, P.E., Thompson, E.J., 1984. The methodology of sister-chromatid exchanges.
humans. International Programme on Chemical Safety. Mutation Research 463, In: Kilbey, B.J., Legator, M., Nichols, W., Ramel, C. (Eds.), Handbook of
111–172. Mutagenicity Test Procedures. Elsevier Science Publishers, Amsterdam, pp.
Arslan, M., Topaktas, M., Rencuzogullari, E., 2008. The effects of boric acid on sister 495–529.
chromatid exchanges and chromosome aberrations in cultured human Prival, J.M., Simmon, F.V., Mortelmans, E.K., 1991. Bacterial mutagenicity testing of
lymphocytes. Cytotechnology 56, 91–96. 49 food ingredients gives very few positive results. Mutation Research 260,
Bolognesi, C., 2003. Genotoxicity of pesticides: a review of human biomonitoring 321–329.
studies. Mutation Research 543, 251–272. _
Rencüzoğullari, E., Ila, H.B., Kayraldiz, A., Topaktasß, M., 2001. Chromosome
Caldecott, K.W., McKeown, C.K., Tucker, J.D., Ljungquist, S., Thompson, L.H., 1994. An aberrations and sister chromatid exchanges in cultured human lymphocytes
interaction between the mammalian DNA repair protein XRCC1 and DNA ligase treated with sodium metabisulfite, a food preservative. Mutation Research 490,
III. Molecular and Cellular Biology 14, 68–76. 107–112.
Çelik, A., 2006. The assessment of genotoxicity of carbamazepine using cytokinesis- Rojas, E., Lopez, M.C., Valverde, M., 1999. Single cell gel electrophoresis assay:
block (CB) micronucleus assay in cultured human blood lymphocytes. Drug and methodology and applications. Journal of Chromatography B 722, 225–254.
Chemical Toxicology 29, 227–236. Saad, B., Bari, M.F., Saleh, M.I., Ahmad, K., Talib, M.K.M., 2005. Simultaneous
Collins, A.R., Dobson, V.L., Dusinská, M., Kennedy, G., Stětina, R., 1997. The comet determination of preservatives (benzoic acid, sorbic acid, methylparaben and
assay: what can it really tell us? Mutation Research 375, 183–193. propylparaben) in foodstuffs using high-performance liquid chromatography.
Council Directive 89/107/EEC of 21 December 1988 on the approximation of the Journal of Chromatography A 1073, 393–397.
laws of the member states concerning food additives authorized for use in Sarıkaya, R., Solak, K., 2003. Benzoik Asit’in Drosophila melanogaster’ de Somatik
foodstuffs intended for human consumption. Official Journal of the European Mutasyon ve Rekombinasyon Testi ile Genotoksisitesinin Arasßtırılması. GÜ Gazi
Communities (L40) of 11 February 1989, pp. 27–33. Eğitim Fakültesi Dergisi 23, 19–32.
Doğruyol, H., 2006. Gıdalardaki katkı maddeleri ve zararları; çocukluk Sasaki, F.Y., Kawaguchi, S., Kamaya, A., Ohshita, M., Kabasawa, K., Iwama, K.,
hiperaktivitesi. Güncel Pediatri 2, 42–48. Taniguchi, K., Tsuda, S., 2002. The comet assay with 8 mouse organs: results
Egger, J., Graham, P.J., Carter, C.M., Gumley, D., Soothill, J.F., 1985. Controlled trial of with 39 currently used food additives. Mutation Research 519, 103–119.
oligoantigenic treatment in the hyperkinetic syndrome. The Lancet 325, 540– Scarfi, M.R., Lioi, M.B., Noce, M.D., Zeni, O., Franceschi, C., Monti, D., Castellani, G.,
545. Bersani, F., 1997. Exposure to 100 Hz pulsed magnetic fields increases
Evans, H.J., 1984. Human peripheral blood lymphocytes for the analysis of micronucleus frequency and cell proliferation in human lymphocytes.
chromosome aberrations in mutagen tests. In: Kilbey, B.J., Legator, M., Bioelectrochemistry 43, 77–81.
Nichols, W., Ramel, C. (Eds.), Handbook of Mutagenicity Test Procedures. Schneider, E.L., Nakanishi, Y., Lewis, J., Sternberg, H., 1981. Simultaneous
Elsevier Science Publishers, Amsterdam, pp. 405–427. examination of sister-chromatid exchanges and cell replication kinetics in
Feingold, B.F., 1973. Food additives and child development. Hospital Practise 21 tumor and normal cells in vivo. Cancer Research 41, 4973–4975.
(11–12), 17–18. Singh, N.P., McCoy, M.T., Tice, R.R., Schneider, E.L., 1988. A simple technique for
Fenech, M., 2000. The in vitro micronucleus technique. Mutation Research 455, 81– quantification of low levels of DNA damage in individual cells. Experimental
95. Cell Research 175, 184–191.
Food Intolerance and Food Aversion, 1984. Food intolerance and food aversion: a Sinues, B., Sanz, A., Bernal, M.L., Tres, A., Alcala, A., Lanuza, J., Ceballos, C., Saenz,
joint report of the royal college of physicians and the British nutrition M.A., 1991. Sister-chromatid exchanges, proliferating rate index, and
foundation. Journal of the Royal College of Physicians of London 18 (2) (April). micronuclei in biomonitoring of internal exposure to vinyl chloride monomer
Fucic, A., Markucic, D., Mijic, A., Jazbec, A.M., 2000. Estimation of genome damage in plastic industry workers. Toxicology and Applied Pharmacology 108, 37–45.
after exposure to ionizing radiation and ultrasound used in industry. Smith, J.M., 1991. Adverse reactions to food and drug additives. European Journal of
Environmental and Molecular Mutagenesis 36, 47–51. Clinical Nutrition 45, 17–21.
Gisselsson, D., 2001. Chromosomal instability in cancer: causes and consequences. Speit, G., Houpter, S., 1985. On the mechanisms of differential giemsa staining of
Atlas of Genetics and Cytogenetics in Oncology and Haematology. Available bromodeoxyuridine-substituted chromosomes. II. Differences between the
from: <http://AtlasGeneticsOncology.org/Deep/ChromosomInstabillD20023. demonstrations of sister-chromatid differentiation and replication patterns.
html>. Human Genetics 70, 126–129.
Goode, E.L., Ulrich, C.M., Potter, J.D., 2002. Polymorphisms in DNA repair genes and Surrales, J., Xamena, N., Creus, A., Catalan, J., Norppa, H., Marcos, R., 1995. Induction
associations with cancer risk. Cancer Epidemiology, Biomarkers and Prevention of micronuclei by five pyrethroid insecticides in whole blood and isolated
11, 1513–1530. human lymphocytes cultures. Mutation Research 341, 169–184.
Hagmar, L., Brogger, A., Hansteen, I.L., Heim, S., Hogstedt, B., Knudsen, L., Lambert, Tamaro, M., Dolzani, L., Monti-Bragadin, C., Sava, G., 1986. Mutagenic activity of the
B., Linnainmaa, K., Mitelman, F., Nordenson, I., Reuterwall, C., Salomaa, S.I., dacarbazine analog p-(3,3-dimethyl-1-triazeno) benzoic acid potassium salt in
Skerfving, S., Sorsa, M., 1994. Cancer risk in human predicted by increased levels bacterial cells. Pharmacological Research Communications 18, 491–501.
of chromosomal aberrations in lymphocytes: Nordic Study Group on the Health Tuormaa, T.E., 1994. The adverse effects of food additives on health: a review of the
Risk of Chromosome Damage. Cancer Research 54, 2919–2922. literature with special emphasis on childhood hyperactivity. Journal of
Hartmann, A., Agurell, E., Beevers, C., Brendler-Schwaab, S., Burlinson, B., Clay, P., Orthomolecular Medicine 9, 225–243.
Collins, A., Smith, A., Speit, G., Thybaud, V., Tice, R.R., 2003. Recommendations Türkoğlu, S., 2007. Genotoxicity of five food preservatives tested on root tips of
for conducting the in situ alkaline Comet assay. Mutagenesis 18, 45–51. Allium cepa L. Mutation Research 626, 4–14.
Hidalgo, A., Gonzalez-Reyes, J.A., Navas, P., Garcia-Herdugo, G., 1989. Abnormal Vernole, P., Caporossi, D., Tedeschi, B., Porfirio, B., Melino, G., Bonmasar, E., Nicoletti,
mitosis and growth inhibition in Allium cepa roots induced by propham and B., 1987. Cytogenetic effects of 1-p-(3-methyltriazeno) benzoic acid potassium
chlorpropham. Cytobios 57, 7–14. salt on human lymphocytes in vitro. Mutation Research 189, 349–356.
N. Zengin et al. / Food and Chemical Toxicology 49 (2011) 763–769 769
Vernole, P., Caporossi, D., Tedeschi, B., Melino, G., Porfirio, B., Bonmasar, E., Yavuz-Kocaman, A., Rencuzogullari, E., Ila, H.B., Topaktas, M., 2008. The genotoxic
Nicoletti, B., 1988. Sister-chromatid exchanges in human lymphocytes effect of potassium metabisulfite using chromosome aberration, sister
exposed to 1-p-(3-methyltriazeno) benzoic acid potassium salt. Mutation chromatid exchange, micronucleus tests in human lymphocytes and
Research 208, 233–236. chromosome aberration test in bone marrow cells of rats. Environmental and
Vidal, A.E., Boiteux, S., Hickson, I.D., Radicella, J.P., 2001. XRCC1 coordinates the Molecular Mutagenesis 49, 276–282.
initial and late stages of DNA abasic site repair through protein–protein Yılmaz, S., Ünal, F., Aksoy, H., Yüzbasßıoğlu, D., Çelik, M., 2008a. Cytogenetic effects of
interactions. The EMBO Journal 20, 6530–6539. citric acid and benzoic acid on Allium chromosomes. Fresenius Environmental
Wang, H., Rosidi, B., Perrault, R., Wang, M., Zhang, L., Windhofer, F., Iliakis, G., 2005. Bulletin 17, 1029–1037.
DNA ligase III as a candidate component of backup pathways of nonhomologous Yılmaz, S., Ünal, F., Yüzbasßıoğlu, D., Aksoy, H., 2008b. Clastogenic effects of food
end joining. Cancer Research 65, 4020–4030. additive citric acid in human peripheral lymphocytes. Cytotechnology 56, 137–
Xing, W., Zhang, Z., 1990. A comparison of SCE test in human lymphocytes and Vicia 140.
faba: a hopeful technique using plants to detect mutagens and carcinogens. Yılmaz, S., Ünal, F., Yüzbasßıoğlu, D., 2009. The in vitro genotoxicity of benzoic acid in
Mutation Research 241, 109–113. human peripheral blood lymphocytes. Cytotechnology 60, 55–61.
Yager, J.W., Paradisin, W.M., Rappaport, S.M., 1993. Sister-chromatid exchanges in Yüzbasßıoğlu, D., Çelik, M., Yılmaz, S., Ünal, F., Aksoy, H., 2006. Clastogenicity of the
lymphocytes are increased in relation to longitudinally measured occupational fungicide afugan in cultured human lymphocytes. Mutation Research 604, 53–
exposure to low concentrations of styrene. Mutation Research 319, 155–165. 59.
Note: This service is not intended for secure transactions such as banking, social media, email, or purchasing. Use at your own risk. We assume no liability whatsoever for broken pages.
Alternative Proxies: