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An in vivo assessment of the genotoxic potential of bisphenol A and 4-tert-octylphenol in rats

  • Genotoxicity and Carcinogenicity
  • Published:
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Abstract

Bisphenol A (BPA) and octylphenol (OP) are industrial chemicals used in the manufacture of polycarbonate plastics, epoxy resins, and non-ionic surfactants. In the present study, we investigated the possible in vivo genotoxic effects of these compounds in rats using single-cell gel electrophoresis, the so-called comet assay. Adult male Wistar albino rats were divided randomly into six groups as follows: BPA125 (received 125 mg/kg bw BPA; n = 6), OP125 (received 125 mg/kg bw OP; n = 6), BPA250 (received 250 mg/kg BPA; n = 6), OP250 (received 250 mg/kg bw OP; n = 6), control (n = 5), and MMS (positive control group that received methyl methanesulfonate; n = 3). Both BPA and OP were orally administrated for 4 weeks. Controls were orally inoculated with corn oil for 4 weeks as well. Comet parameters including tail length and tail moment were evaluated for possible genotoxic effects. There were no significant differences in the OP125 and in the BPA125 compared with the control group, regarding tail length and tail moment (P > 0.05). However, there were significant differences in the OP250 and in the BPA250 compared with the control group, regarding tail length and tail moment (P < 0.05 and P < 0.01, respectively). The genotoxic potential of BPA and OP was investigated in vivo; there is a need for further studies exploring further mechanisms of the genotoxic potential of these chemicals in vivo.

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References

  • Andersen M, Kiel P, Larsen H, Maxild J (1978) Mutagenic action of aromatic epoxy resins. Nature 276:391–392

    Article  PubMed  CAS  Google Scholar 

  • Aydogan M, Barlas N (2006) Effects of maternal 4-tert-octylphenol exposure on the reproductive tract of male rats at adulthood. Reprod Toxicol 22:455–460

    Article  PubMed  CAS  Google Scholar 

  • Bhat HK, Calaf G, Hei TK, Loya T, Vadgama JV (2003) Critical role of oxidative stress in estrogen-induced carcinogenesis. Proc Natl Acad Sci USA 100:3913–3928

    Article  PubMed  CAS  Google Scholar 

  • Blackburn MA, Walddock MJ (1995) Concentrations of alkylphenols in rivers and estuaries in England and Wales. Water Res 29:1623–1629

    Article  CAS  Google Scholar 

  • Boockfor FR, Blake CA (1997) Chronic administration of 4-tert-octylphenol to adult male rats causes shrinkage of the testes and male accessory sex organs, disrupts spermatogenesis and increases the incidence of sperm deformities. Biol Reprod 57:267–277

    Article  PubMed  CAS  Google Scholar 

  • Brix R, Postigo C, González S, Villagrasa M, Navarro A, Kuster M, de Alda MJ, Barceló D (2010) Analysis and occurrence of alkylphenolic compounds and estrogens in a European river basin and an evaluation of their importance as priority pollutants. Anal Bioanal Chem 396:1301–1309

    Article  PubMed  CAS  Google Scholar 

  • Cabaton N, Dumont C, Severin I, Perdu E, Zalko D, Cherkaoui-Malki M, Chagnon MC (2009) Genotoxic and endocrine activities of bis(hydroxyphenyl)methane (bisphenol F) and its derivatives in the HepG2 cell line. Toxicol 255:15–24

    Article  CAS  Google Scholar 

  • Calafat AM, Kuklenyik Z, Reidy JA, Caudill SP, Ekong J, Needham LL (2005) Urinary concentrations of bisphenol A and 4-nonylphenol in a human reference population. Environ Health Perspect 113:391–395

    Article  PubMed  CAS  Google Scholar 

  • Cavalieri E, Frenkel K, Liehr JG, Rogan E, Roy D (2000) Estrogens as endogenous genotoxic agents-DNA adducts and mutations. J Natl Cancer Inst Monogr 27:75–93

    PubMed  CAS  Google Scholar 

  • Cavalieri EL, Li KM, Balu N, Saeed M, Devanesan P, Higginbotham S, Zhao JML, Gross Rogan EG (2002) Catechol ortho-quinones: the electrophilic compounds that form depurinating DNA adducts and could initiate cancer and other diseases. Carcinogenesis 23:1071–1077

    Article  PubMed  CAS  Google Scholar 

  • Chen Y, Liu X, Pisha E, Constantinou AI, Hua Y, Shen L, van Breemen RB, Elguindi EC, Blond SY, Zhang F, Bolton JL (2000) A metabolite of equine estrogens, 4-hydroxyequilenin, induces DNA damage and apoptosis in breast cancer cell lines. Chem Res Toxicol 13:342–350

    Article  PubMed  CAS  Google Scholar 

  • Dachs J, Vanry DA, Eisenreich SJ (1999) Occurence of estrogenic nonylphenols in the urban and coastal atmosphere of the lower Hudson river estuary. Environ Sci Technol 33:2676–2679

    Article  CAS  Google Scholar 

  • Dukes PP, Goldwasser E (1961) Inhibition of erythropoiesis by estrogens. Endocrinology 69:21–29

    Article  PubMed  CAS  Google Scholar 

  • EFSA (2006) Opinion of the scientific panel on food additives, flavourings, processing aids and materials in contact with food on a request from the commission related to 2, 2-bis(4-hydroxyphenyl)propane (bisphenol A). EFSA J 428:1–75

    Google Scholar 

  • Elia MC, Storer RD, Harmon LS, Kraynak AR, McKelvey TW, Hertzog PR, Keenan KP, DeLuca JG, Nichols WW (1993) Cytotoxicity as measured by trypan blue as a potentially confounding variable in the in vitro alkaline elusion/rat hepatocyte assay. Mutat Res 291:193–205

    PubMed  CAS  Google Scholar 

  • Göktekin E, Barlas N (2008) Histopathological effects of 4-tert-octylphenol treatment through the pregnancy period, on the pituitary, adrenal, pancreas, thyroid and parathyroid glands of offspring rats at adulthood. Environ Toxic and Pharm 26:199–205

    Article  Google Scholar 

  • Gudi R, Xu J, Thilagar A (1992) Assessment of the in vivo aneuploidy/micronucleus assay in mouse bone marrow cells with 16 chemicals. Environ Mol Mutagen 20:106–116

    Article  PubMed  CAS  Google Scholar 

  • Haighton LA, Hlywka JJ, Doull J, Kroes R, Lynch BS, Munro IC (2002) An evaluation of the possible carcinogenicity of bisphenol A to humans. Regul Toxicol Pharmacol 35:238–254

    Article  PubMed  CAS  Google Scholar 

  • Hartman A, Speit G (1995) Genotoxic effects of chemicals in the SCG test. Mutat Res 346:49–56

    Article  Google Scholar 

  • Hartman A, Speit G (1997) The contribution of cytotoxicity to DNA effects in the single cell gel test (comet assay). Toxicol Lett 90:183–188

    Article  Google Scholar 

  • Hartman A, Kiskinis E, Fjallman A, Suter W (2001) Influence of cytotoxicity and compound precipitation on test results in the alkaline comet assay. Mutat Res 497:199–212

    Google Scholar 

  • Hashimoto K, Nakajima Y, Matsumura S, Chatani F (2010) An in vitro micronucleus assay with size-classified micronucleus counting to discriminate aneugens from clastogens. Toxicol In Vitro 24:208–216

    Article  PubMed  CAS  Google Scholar 

  • Henderson L, Wolfreys A, Fedyk J, Bourner C, Windebank S (1998) The ability of the comet assay to discriminate between genotoxins and cytotoxins. Mutagenesis 13:89–94

    Article  PubMed  CAS  Google Scholar 

  • Ikezuki Y, Tsutsumi O, Takai Y, Kamei Y, Taketani Y (2002) Determination of bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure. Hum Reprod 17:2839–2841

    Article  PubMed  CAS  Google Scholar 

  • Iso T, Watanabe T, Iwamoto T, Shimamoto A, Furuichi Y (2006) DNA damage caused by bisphenol A and estradiol through estrogenic activity. Biol Pharm Bull 29:206–210

    Article  PubMed  CAS  Google Scholar 

  • Johnson GE, Parry EM (2008) Mechanistic investigations of low dose exposures to the genotoxic compounds Bisphenol-A and rotenone. Mutat Res 651:56–63

    PubMed  CAS  Google Scholar 

  • Kabuto H, Hasuike S, Minagawa N, Shishibori T (2003) Effects of bisphenol A on the metabolisms of active oxygen species in mouse tissues. Environ Res 93:31–35

    Article  PubMed  CAS  Google Scholar 

  • Knaak J, Sullivan LJ (1966) Metabolism of bisphenol A in the rat. Toxicol Appl Pharmacol 8:175–184

    Article  PubMed  CAS  Google Scholar 

  • Kuch HM, Ballschmiter K (2001) Determination of endocrine-disrupting phenolic compounds and estrogens in surface and drinking water by HRGC-(NCI)-MS in the pictogram per liter range. Environ Sci Technol 35:3201–3206

    Article  PubMed  CAS  Google Scholar 

  • Lee M, Kwon J, Chunk MK (2003) Enhanced prediction of potential rodent carcinogenicity by utilizing comet assay and apoptotic assay in combination. Mutat Res 541:9–19

    PubMed  CAS  Google Scholar 

  • Liehr JG (2000) Is estradiol a genotoxic mutagenic carcinogen? Endocr Rev 21:40–54

    Article  PubMed  CAS  Google Scholar 

  • Lu B, Zhan P (2008) Effects of nonylphenol on the brain development-associated gene expression profiles of F1 generation rats. Toxicol Environ Chem 90:127–143

    Article  CAS  Google Scholar 

  • Milman HA, Bosland MC, Walden PD, Heinze JE (2002) Evaluation of the adequacy of published studies of low-dose effects of bisfenol A on the rodent prostate for use in human risk assessment. Reg Toxicol Pharm 35:338–346

    Article  CAS  Google Scholar 

  • Miyamae Y, Rojas E, Ryu JC, Sakai YF (2000) The single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 35:206–221

    Article  PubMed  Google Scholar 

  • Mobley JA, Brueggemeier RW (2004) Estrogen receptor-mediated regulation of oxidative stress and DNA damage in breast cancer. Carcinogenesis 25:3–9

    Article  PubMed  CAS  Google Scholar 

  • Naik P, Vijayalaxmi KK (2009) Cytogenetic evaluation for genotoxicity of bisphenol-A in bone marrow cells of Swiss albino mice. Mutat Res 676:106–112

    PubMed  CAS  Google Scholar 

  • National Toxicology Program (1982) Carcinogenesis bioassay of bisphenol A in F344 rats and B6C3F mice. National Toxicology Program Technical Report 215:1–116

    Google Scholar 

  • Olive PL, Banath JP (1995) Sizing highly fragmented DNA in individual apoptotic cells using the comet assay and a DNA crosslinking agent. Exp Cell Res 221:19–26

    Article  PubMed  CAS  Google Scholar 

  • Oshida K, Iwanaga E, Miyamoto-Kuramitsu K, Miyamoto Y (2008) An in vivo comet assay of multiple organs (liver, kidney and bone marrow) in mice treated with methyl methanesulfonate and acetaminophen accompanied by hematology and/or blood chemistry. J Toxicol Sci 33:515–524

    Article  PubMed  CAS  Google Scholar 

  • Pacchierotti E, Ranaldi R, Eichenlaub-Titter U, Attia S, Adler ID (2008) Evaluation of aneugenic effects of Bisphenol-A in somatic and germ cells of mouse. Mutat Res 651:64–70

    PubMed  CAS  Google Scholar 

  • Park SY, Choi J (2009) Genotoxic effects of nonylphenol and bisphenol A exposure in aquatic biomonitoring species: freshwater crustacean, Daphnia magna, and aquatic midge, Chironomus riparius. Bull Environ Contam Toxicol 83:463–468

    Article  PubMed  CAS  Google Scholar 

  • Quiros L, Cespedes R, Lacorte S, Viana P, Raldua D (2005) Detection and evaluation of endocrine-disruption activity in water samples from Portuguese rivers. Environ Toxicol Chem 24:389–395

    Article  PubMed  CAS  Google Scholar 

  • Reed HBW (1978) Alkylphenols. In: Grayson M, Eckroth D (eds) Kirk-othmer encyclopedia of chemical technology. Wiley-Liss Inc, New York, pp 72–96

    Google Scholar 

  • Roser S, Pool-Zobel BL, Rechkemmer G (2001) Contribution of apoptosis to responses in the comet assay. Mutat Res 497:169–175

    PubMed  CAS  Google Scholar 

  • Schönfelder G, Wittfoht W, Hopp H, Talsness CE, Paul M, Chahoud I (2002) Parent bisphenol A accumulation in the human maternal-fetal-placental unit. Environ Health Perspect 110:A703–A707

    Article  PubMed  Google Scholar 

  • Schweikl H, Schmalz G, Rackebrandt K (1998) The mutagenic activity of unpolymerized resin monomers in Salmonella typhimurium and V79 cells. Mutat Res 415:119–130

    PubMed  CAS  Google Scholar 

  • Tayama S, Nakagawa Y, Tayama K (2008) Genotoxic effects of environmental estrogen-like compounds in CHO-K1 cells. Mutat Res 649:114–125

    PubMed  CAS  Google Scholar 

  • Tice RR, Agurell E, Anderson D, Burlinson B, Hartmann A, Kobayashi H, Raychoundhury SS, Blake CA, Millette CF (1999) Toxic effects of octylphenol on cultured rat spermatogenic cells and Sertoli cells. Toxicol Appl Pharm 157:192–202

    Article  Google Scholar 

  • Tice RR, Agurell E, Anderson D, Burlinson B, Hartmann A, Kobayashi H, Miyamae Y, Rojas E, Ryu JC, Sasaki YF (2000) Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 35:206–221

    Article  PubMed  CAS  Google Scholar 

  • Toppari J, Larsen JC, Christiansen P, Giwercman A, Grandjean P, Guillette LJ Jr, Jégou B, Jensen TK, Jouannet P, Keiding N, Leffers H, McLachlan JA, Meyer O, Müller J, Rajpert-De Meyts E, Scheike T, Sharpe R, Sumpter J, Skakkebaek NE (1996) Male reproductive health and environmental xenoestrogens. Environ Health Perspect 104:741–803

    PubMed  CAS  Google Scholar 

  • Toppari J, Kaleva M, Virtanen HE (2001) Trends in the incidence of cryptorchidism and hypospadias, and methodological limitations of registry-based data. Hum Reprod Update 7:282–286

    Article  PubMed  CAS  Google Scholar 

  • Upmeier A, Degen HG, Diel P, Michna H, Bolt HM (2000) Toxicokinetics of bisfenol A in female DA/Han rats after a single i.v. and oral administration. Arch Toxicol 74:431–436

    Article  PubMed  CAS  Google Scholar 

  • Voutsa D, Hartmann P, Schaffner C, Giger W (2006) Benzotriazoles, alkylphenols and bisphenol A in municipal wastewaters and in the Glatt River, Switzerland. Environ Sci Pollut Res Int 13:333–341

    Article  PubMed  CAS  Google Scholar 

  • Xie Z, Selzer J, Ebinghaus R, Caba A, Ruck W (2006) Development and validation of a method for the determination of trace alkylphenols and phthalates in the atmosphere. Anal Chim Acta 565:198–207

    Article  CAS  Google Scholar 

  • Ying GG, Williams B, Kookana R (2002) Environmental fate of alkylphenols and alkylphenol ethoxylates―a review. Environ Int 28:215–226

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This research was partially supported by the Scientific Research Unit of University of Hacettepe (Project No. 09 D05 601 002).

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Correspondence to Nurhayat Barlas.

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Ulutaş, O.K., Yıldız, N., Durmaz, E. et al. An in vivo assessment of the genotoxic potential of bisphenol A and 4-tert-octylphenol in rats. Arch Toxicol 85, 995–1001 (2011). https://doi.org/10.1007/s00204-010-0620-y

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  • DOI: https://doi.org/10.1007/s00204-010-0620-y

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