Mutagenicity and DNA Damage of Bisphenol a and its Structural Analogues in Hepg2 Cells

Fic, Anja; Žegura, Bojana; Sollner Dolenc, Marija; Filipič, Metka; Peterlin Mašič, Lucija

doi:10.2478/10004-1254-64-2013-2319

Abstract

Environmental oestrogen bisphenol A (BPA) and its analogues are widespread in our living environment. Because their production and use are increasing, exposure of humans to bisphenols is becoming a significant issue. We evaluated the mutagenic and genotoxic potential of eight BPA structural analogues (BPF, BPAF, BPZ, BPS, DMBPA, DMBPS, BP-1, and BP-2) using the Ames and comet assay, respectively. None of the tested bisphenols showed a mutagenic effect in Salmonella typhimurium strains TA98 and TA100 in either the presence or absence of external S9-mediated metabolic activation (Aroclor 1254-induced male rat liver). Potential genotoxicity of bisphenols was determined in the human hepatoma cell line (HepG2) at non-cytotoxic concentrations (0.1 μmol L^-1to 10 μmol L^-1) after 4-hour and 24-hour exposure. In the comet assay, BPA and its analogue BPS induced significant DNA damage only after the 24-hour exposure, while analogues DMBPS, BP-1, and BP-2 induced a transient increase in DNA strand breaks

References

1. World Health Organization (WHO). Joint FAO/WHO Expert Meeting to Review Toxicological and Health Aspects of Bisphenol A [displayed 30 May 2011]. Available at http:// www.who.int/entity/foodsafety/chem/chemicals/BPA_Summary2010.pdf
Search in Google Scholar
2. Maffini MV, Rubin BS, Sonnenschein C, Soto AM. Endocrine disruptors and reproductive health: The case of bisphenol-A. Mol Cell Endocrinol 2006;254:179-86.10.1016/j.mce.2006.04.033
Search in Google Scholar
3. Rasier G, Toppari J, Parent AS, Bourguignon JP. Female sexual maturation and reproduction after prepubertal exposure to estrogens and endocrine disrupting chemicals: A review of rodent and human data. Mol Cell Endocrinol 2006;254:187-201.10.1016/j.mce.2006.04.002
Search in Google Scholar
4. Screening Assessment for the Challenge Phenol, 4,4’ -(1- methylethylidene)bis- (Bisphenol A).Chemical Abstracts Service Registry Number 80-05-7. Environment Canada 2008 [displayed 11 Sept 2012]. Available at http://www.ec.gc.ca/ese-ees/3C756383-BEB3-45D5-B8D3-E8C800F35243/batch2_80-05-7_en.pdf
Search in Google Scholar
5. Appleton. Nation’s Largest Maker of Thermal Receipt Paper Does Not Use BPA [displayed at 23 May 2013]. Available at http://www.appletonideas.com/pdf/Appleton%20BPA%20free%20news%20release.7.27.2010.pdf
Search in Google Scholar
6. EU directive 2011/8/EU. Commission directive 2011/8/EU of 28 January 2011. [displayed 3 June 2011]. Available at http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ: L:2011:026:0011:0014:EN:PDF
Search in Google Scholar
7. Chen MY, Ike M, Fujita M. Acute toxicity, mutagenicity, and estrogenicity of bisphenol-A and other bisphenols. Environ Toxicol 2002;17:80-6. doi: 10.1002/tox.1003510.1002/tox.10035
Search in Google Scholar
8. Kuruto-Niwa R, Nozawa R, Miyakoshi T, Shiozawa T, Terao Y. Estrogenic activity of alkylphenols, bisphenol S, and their chlorinated derivatives using a GFP expression system. Environ Toxicol Pharmacol 2005;19:121-30. doi: 10.1016/ j.etap10.1016/j.etap.2004.05.009
Search in Google Scholar
9. Raloff J. Receipts a large - and largely ignored - source of BPA. ScienceNews.org. [displayed 30 August 2010]. Available at http://www.sciencenews.org/view/generic/id/61764/title/Receipts_a_large_%E2%80%94_and_largely_ignored_%E2%80%94_source_of_BPA
Search in Google Scholar
10. Danzl E, Sei K, Soda S, Ike M, Fujita M. Biodegradation of bisphenol A, bisphenol F and bisphenol S in Seawater. Int J Environ Res Public Health 2009;6:1472-84. doi: 10.3390/ ijerph604147210.3390/ijerph6041472
Search in Google Scholar
11. Ike M, Chen MY, Danzl E, Sei K, Fujita M. Biodegradation of a variety of bisphenols under aerobic and anaerobic conditions. Water Sci Technol 2006;53:153-9. doi: 10.3390/ ijerph604147210.2166/wst.2006.189
Search in Google Scholar
12. US Patent. 1978. 4,098,769 [displayed 8 December 2011]. Available at http://www.patents.com/us-4098769.html
Search in Google Scholar
13. Lotti N, Colonna M, Fiorini M, Finelli L, Berti C. Poly(butylene terephthalate) modified with ethoxylated bisphenol S with increased glass transition temperature and improved thermal stability. Polymer 2011;52:904-11. doi: 10.1016/j.polymer.2011.01.01810.1016/j.polymer.2011.01.018
Search in Google Scholar
14. Kitamura S, Suzuki T, Sanoh S, Kohta R, Jinno N, Sugihara K, Yoshihara S, Fujimoto N, Watanabe H, Ohta S. Comparative Study of the Endocrine-Disrupting Activity of Bisphenol A and 19 Related Compounds. Toxicol Sci 2005;84:249-59. doi: 10.1093/toxsci/kfi07410.1093/toxsci/kfi074
Search in Google Scholar
15. Tsutsui T, Tamura Y, Suzuki A, Hirose Y, Kobayashi M, Nishimura H, Metzler M, Barrett JC. Mammalian cell transformation and aneuploidy induced by five bisphenols. Int J Cancer 2000;86:151-4. doi: 10.1002/(SICI)1097-0215(20000415)86:2<;151::AID-IJC1>3.0.CO;2-010.1002/(SICI)1097-0215(20000415)86:2<;151::AID-IJC1>3.0.CO;2-0
Search in Google Scholar
16. National Toxicology Program (NTP). Chemical Information Profile for Bisphenol AF [CAS No. 1478-61-1], Supporting Nomination for Toxicological Evaluation by the National Toxicology Program [displayed 30 March 2011]. Available at http://ntp.niehs.nih.gov/ntp/htdocs/Chem_Background/ExSumPdf/BisphenolAF_093008_508.pdf
Search in Google Scholar
17. Doherty LF, Bromer JG, Zhou Y, Aldad TS, Taylor HS. In utero exposure to diethylstilbestrol (DES) or bisphenol-A (BPA) increases EZH2 expression in the mammary gland: an epigenetic mechanism linking endocrine disruptors to breast cancer. Horm Cancer 2010;1:146-55. doi: 10.1007/ s12672-010-0015-910.1007/s12672-010-0015-9
Search in Google Scholar
18. International Agency for Research on Cancer (IARC). International Agency for Research on Cancer, Sex Hormones (II). IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Vol. 21. Lyon: IARC; 1979.
Search in Google Scholar
19. ChemBio3D Ultra 13.0 [Computer software] in ChemBioOfficeR Ultra 13.0, PerkinElmer, www. cambridgesoft.com/, Release Date: August, 2012.
Search in Google Scholar
20. Ashby J, Tennant RW. Chemical-structure, Salmonella mutagenicity and extent of carcinogenicity as indicators of genotoxic carcinogenesis among 222 chemicals tested in rodents by the United-States NCI/NTP. Mutat Res 1988;204:17-115.10.1016/0165-1218(88)90114-0
Search in Google Scholar
21. Schweikl H, Schmalz G, Rackebrandt K. The mutagenic activity of unpolymerized resin monomers in Salmonella typhimurium and V79 cells. Mutat Res 1998;415:119-30.10.1016/S1383-5718(98)00067-9
Search in Google Scholar
22. Tsutsui T, Tamura Y, Yagi E, Hasegawa K, Takahashi M, Maizumi N, Yamaguchi F, Barrett JC. Bisphenol-A induces cellular transformation, aneuploidy and DNA adduct formation in cultured Syrian hamster embryo cells. Int J Cancer 1998;75:290-4. doi: 10.1002/(SICI)1097-0215(19980119)75:2<;290::AID-IJC19>3.0.CO;2-H10.1002/(SICI)1097-0215(19980119)75:2<;290::AID-IJC19>3.0.CO;2-H
Search in Google Scholar
23. Ivett JL, Brown BM, Rodgers C, Anderson BE, Resnick MA, Zeiger E. Chromosomal aberrations and sister chromatid exchange tests in Chinese hamster ovary cells in vitro. IV. Results with 15 chemicals. Environ Mol Mutagen 1989;14:165-87. doi: 10.1002/em.285014030610.1002/em.2850140306
Search in Google Scholar
24. Naik P, Vijayaaxmi KK. Cytogenetic evaluation for genotoxicity of Bisphenol-A in bone marrow cells of Swiss albino mice. Mutat Res 2009;676:106-12. doi: 10.1016/ j.mrgentox.2009.04.01010.1016/j.mrgentox.2009.04.010
Search in Google Scholar
25. Atkinson A, Roy D. In vitro conversion of environmental estrogenic chemical bisphenol A to DNA binding metabolite(s). Biochem Biophys Res Commun 1995;210:424-33.10.1006/bbrc.1995.1678
Search in Google Scholar
26. Edmonds JS, Nomachi M, Terasaki M, Morita M, Skelton BW, White AH. The reaction of bisphenol A 3,4-quinone with DNA. Biochem Biophys Res Commun 2004;319:556-61. doi: 10.1016/j.bbrc.2004.05.02410.1016/j.bbrc.2004.05.024
Search in Google Scholar
27. Atkinson A, Roy D. In vivo DNA adduct formation by bisphenol A. Environ Mol Mutagen 1995;26:60-6. doi: 10.1002/em.285026010910.1002/em.2850260109
Search in Google Scholar
28. Izzotti A, Kanitz S, D’Agostini F, Camoirano A, De Flora S. Formation of adducts by bisphenol A, an endocrine disruptor, in DNA in vitro and in liver and mammary tissue of mice. Mutat Res 2009;679:28-32. doi: 10.1016/j. mrgentox.2009.07.011
Search in Google Scholar
29. Iso T, Watanabe T, Iwamoto T, Shimamoto A, Furuichi Y. DNA damage caused by bisphenol A and estradiol through estrogenic activity. Biol Pharm Bull 2006;29:206-10. doi:10.1248/bpb.29.20610.1248/bpb.29.206
Search in Google Scholar
30. Cabaton N, Dumont C, Severin I, Perdu E, Zalko D, Cherkaoui-Malki M, Chagnon MC. Genotoxic and endocrine activities of bis(hydroxyphenyl)methane (bisphenol F) and its derivatives in the HepG2 cell line. Toxicology 2009;255:15-24. doi: 10.1016/j.tox.2008.09.02410.1016/j.tox.2008.09.024
Search in Google Scholar
31. Audebert M, Dolo L, Perdu E, Cravedi JP, Zalko D. Use of the gamma H2AX assay for assessing the genotoxicity of bisphenol A and bisphenol F in human cell lines. Arch Toxicol 2011;85:1463-73. doi: 10.1007/s00204-011-0721-210.1007/s00204-011-0721-2
Search in Google Scholar
32. Pfeiffer E, Rosenberg B, Deuschel S, Metzler M. Interference with microtubules and induction of micronuclei in vitro by various bisphenols. Mutat Res 1997;390:21-31.10.1016/S0165-1218(96)00161-9
Search in Google Scholar
33. Kanai H, Barrett JC, Metzler M, Tsutsui T. Cell-transforming activity and estrogenicity of bisphenol-A and 4 of its analogs in mammalian cells. Int J Cancer 2001;93:20-5. doi: 10.1002/ ijc.130310.1002/ijc.1303
Search in Google Scholar
34. Maron DM, Ames BN. Revised methods for the Salmonella mutagenicity test. Mutat Res 1983;113:173-215.10.1016/0165-1161(83)90010-9
Search in Google Scholar
35. Kenyon MO, Cheung JR, Dobo KL, Ku WW. An evaluation of the sensitivity of the Ames assay to discern low-level mutagenic impurities. Regul Toxicol Pharmacol 2007;48:75-86. doi: 10.1016/j.yrtph.2007.01.00610.1016/j.yrtph.2007.01.006
Search in Google Scholar
36. Westerink WM, Schoonen WG. Phase II enzyme levels in HepG2 cells and cryopreserved primary human hepatocytes and their induction in HepG2 cells. Toxicol In Vitro 2007;21:1592-602. doi: 10.1016/j.tiv.2007.06.01710.1016/j.tiv.2007.06.017
Search in Google Scholar
37. Westerink WM, Schoonen WG. Cytochrome P450 enzyme levels in HepG2 cells and cryopreserved primary human hepatocytes and their induction in HepG2 cells. Toxicol In Vitro 2007;21:1581-91. doi: 10.1016/j.tiv.2007.05.01410.1016/j.tiv.2007.05.014
Search in Google Scholar
38. Wilkening S, Stahl F, Bader A. Comparison of primary human hepatocytes and hepatoma cell line Hepg2 with regard to their biotransformation properties. Drug Metab Dispos 2003;31:1035-42. doi: 10.1124/dmd.31.8.103510.1124/dmd.31.8.1035
Search in Google Scholar
39. Hreljac I, Filipič M. Organophosphorus pesticides enhance the genotoxicity of benzo(a)pyrene by modulating its metabolism. Mutat Res 2009;671:84-92. doi: 10.1016/j. mrfmmm.2009.09.011
Search in Google Scholar
40. Knasmuller S, Parzefall W, Sanyal R, Ecker S, Schwab C, Uhl M, Mersch-Sundermann V, Williamson G, Hietsch G, Langer T, Darroudi F, Natarajan AT. Use of metabolically competent human hepatoma cells for the detection of mutagens and antimutagens. Mutat Res 1998;402:185-202.10.1016/S0027-5107(97)00297-2
Search in Google Scholar
41. Solakidi S, Psarra AMG, Sekeris CE. Differential subcellular distribution of estrogen receptor isoforms: Localization of ERα in the nucleoli and ERβ in the mitochondria of human osteosarcoma SaOS-2 and hepatocarcinoma HepG2 cell lines. Biochim Biophys Acta - Mol Cell Res 2005;1745:382-92. doi: 10.1016/j.bbamcr.2005.05.01010.1016/j.bbamcr.2005.05.01015993498
Search in Google Scholar
42. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Meth 1983;65:55-63. doi: 10.1016/0022-1759(83)90303-410.1016/0022-1759(83)90303-4
Search in Google Scholar
43. Žegura B, Zajc I, Lah TT, Filipič M. Patterns of microcystin- LR induced alteration of the expression of genes involved in response to DNA damage and apoptosis. Toxicon 2008;51:615-23. doi: 10.1016/j.toxicon.2007.11.00910.1016/j.toxicon.2007.11.009
Search in Google Scholar
44. Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 1988;175:184-91.10.1016/0014-4827(88)90265-0
Search in Google Scholar
45. Žegura B, Filipič M. Application of in vitro comet assay for genotoxicity testing. In: Yan Z, Caldwell G, editors. Optimization in drug discovery: In vitro methods. Totowa (NJ): Humana Press; 2004. p. 301-13.10.1385/1-59259-800-5:301
Search in Google Scholar
46. Tiwari D, Kamble J, Chilgunde S, Patil P, Maru G, Kawle D, Bhartiya U, Joseph L, Vanage G. Clastogenic and mutagenic effects of bisphenol A: an endocrine disruptor. Mutat Res 2012;743:83-90. doi: doi: 10.1016/j. mrgentox.2011.12.023
Search in Google Scholar
47. Yamaguchi T, Yamauchi A, Yamazaki H, Kakiuchi Y. Mutagenicity of rubber additives in tire. Eisei Kagaku 1991;37:6-13.10.1248/jhs1956.37.6
Search in Google Scholar
48. Japan Chemical Industry Ecology-Toxicology & Information Center (JETOC). Mutagenicity Test Data of Existing Chemical Substances Based on the Toxicity Investigation System of the Industrial Safety and Health Law (I). Tokyo: JETOC; 1996.
Search in Google Scholar
49. National Institute of Environmental Health Sciences (NIH). National Toxicology Program. 2001. National Toxicology Program’s Report of the Endocrine Disruptors Low-Dose Peer Review [displayed 20 Dec 2011]. Available at www. epa.gov/endo/pubs/edmvs/lowdosepeerfinalrpt.pdf
Search in Google Scholar
50. Richter CA, Birnbaum LS, Farabollini F, Newbold RR, Rubin BS, Talsness CE, Vandenbergh JG, Walser-Kuntz DR, vom Saal FS. In vivo effects of bisphenol A in laboratory rodent studies. Reprod Toxicol 2007;24:199-224.10.1016/j.reprotox.2007.06.004
Search in Google Scholar
51. Tice RR, Agurell E, Anderson D, Burlinson B, Hartmann A, Kobayashi H, Miyamae Y, Rojas E, Ryu JC, Sasaki YF. Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 2000;35:206-21.10.1002/(SICI)1098-2280(2000)35:3<;206::AID-EM8>3.0.CO;2-J
Search in Google Scholar
52. Collins AR, Dobson VL, Dušinska M, Kennedy G, Štetina R. The comet assay: what can it really tell us? Mutat Res 1997;375:183-93.
Search in Google Scholar
53. Iso T, Futami K, Iwamoto T, Furuichi Y. Modulation of the expression of Bloom helicase by estrogenic agents. Biol Pharm Bull 2007;30:266-71. doi: 10.1248/bpb.30.26610.1248/bpb.30.266
Search in Google Scholar
54. Cavalieri EL, Rogan EG. Is Bisphenol A a weak carcinogen like the natural estrogens and diethylstilbestrol? IUBMB Life 2010;62:746-51. doi: 10.1002/iub.37610.1002/iub.376
Search in Google Scholar
55. Schmidt J, Kotnik P, Trontelj J, Knez Z, Mašič LP. Bioactivation of bisphenol A and its analogs (BPF, BPAF, BPZ and DMBPA) in human liver microsomes. Toxicol In Vitro 2013;27:1267-76. doi: 10.1016/j.tiv.2013.02.01610.1016/j.tiv.2013.02.016
Search in Google Scholar
56. Jaeg JP, Perdu E, Dolo L, Debrauwer L, Cravedi JP, Zalko D. Characterization of new bisphenol a metabolites produced by CD1 mice liver microsomes and S9 fractions. J Agric Food Chem 2004;52:4935-42. doi: 10.1021/jf049762u10.1021/jf049762u15264938
Search in Google Scholar
57. Nakagawa Y, Suzuki T. Metabolism of bisphenol A in isolated rat hepatocytes and oestrogenic activity of a hydroxylated metabolite in MCF-7 human breast cancer cells. Xenobiotica 2001;31:113-23.10.1080/0049825011004050111465389
Search in Google Scholar
58. Kolšek K, Mavri J, Sollner Dolenc M. Reactivity of bisphenol A-3,4-quinone with DNA. A quantum chemical study. Toxicol in Vitro 2012;26:102-6. doi: 10.1016/j. tiv.2011.11.003
Search in Google Scholar
59. Sakuma S, Nakanishi M, Morinaga K, Fujitake M, Wada S, Fujimoto Y. Bisphenol A 3,4-quinone induces the conversion of xanthine dehydrogenase into oxidase in vitro. Food Chem Toxicol 2010;48:2217-22. doi: 10.1016/j.fct.2010.05.05110.1016/j.fct.2010.05.05120594952
Search in Google Scholar
60. Bursztyka J, Perdu E, Pettersson K, Pongratz I, Fernandez- Cabrera M, Olea N, Debrauwer L, Zalko D, Cravedi JP. Biotransformation of genistein and bisphenol A in cell lines used for screening endocrine disruptors. Toxicol in Vitro 2008;22:1595-604. doi: 10.1016/j.tiv.2008.06.01310.1016/j.tiv.2008.06.01318640261
Search in Google Scholar
61. Tu T, Giblin D, Gross mL. Structural determinant of chemical reactivity and potential health effects of quinones from natural products. Chem Res Toxicol 2011;24:1527-39. doi: 10.1021/tx200140s10.1021/tx200140s317798521721570
Search in Google Scholar

Mutagenicity and DNA Damage of Bisphenol a and its Structural Analogues in Hepg2 Cells

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