DNA damage caused by bisphenol A and estradiol through estrogenic activity.

GeneCare Research Institute Co. Ltd., 200 Kajiwara, Kamakura, Kanagawa 247-0063, Japan.
Biological & Pharmaceutical Bulletin (Impact Factor: 1.78). 03/2006; 29(2):206-10. DOI: 10.1248/bpb.29.206
Source: PubMed

ABSTRACT Evidence exists that raises concern about genotoxic effects induced by estrogen: oxidative stress caused by estrogen-derived oxidants, DNA adducts formed by estrogen metabolites and estrogen-induced chromosomal aberration. Estrogen receptors (ER) participate in some of these genotoxic effects by estrogen. In this study, we showed the effects of bisphenol A (BPA), an endocrine-disrupting chemical eliciting weak estrogenic activity, and of 17beta-estradiol (E2), on DNA damage in ER-positive MCF-7 cells by Comet assay. Higher concentrations of BPA, more than 1000 times of E2, were needed to induce the same levels of effects by E2. Immunofluorescence microscopy showed that gammaH2AX, an early marker of DNA breaks, increased after treatment with E2 or BPA in MCF-7 cells. gammaH2AX foci colocalized with Bloom helicase, which is considered to be responsible for the repair of DNA damage after treatment with E2 or BPA. Interestingly, DNA damage was not as severe in ER-negative MDA-MB-231 cells as in MCF-7 cells. The ER antagonist ICI182780 blocked E2 and BPA genotoxic effects on MCF-7 cells. These results together suggest that BPA causes genotoxicity ER dependently in the same way as E2.

  • Toxicology Letters 06/2012; 211:S61. DOI:10.1016/j.toxlet.2012.03.240 · 3.36 Impact Factor
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    ABSTRACT: Bisphenol A (BPA) is a biologically active industrial chemical used in production of consumer products. BPA has become a target of intense public scrutiny following concerns about its association with human diseases such as obesity, diabetes, reproductive disorders, and cancer. Recent studies link BPA with the generation of reactive oxygen species, and base excision repair (BER) is responsible for removing oxidatively induced DNA lesions. Yet, the relationship between BPA and BER has yet to be examined. Further, the ubiquitous nature of BPA allows continuous exposure of the human genome concurrent with the normal en-dogenous and exogenous insults to the genome, and this co-exposure may impact the DNA damage response and repair. To determine the effect of BPA exposure on base exci-sion repair of oxidatively induced DNA damage, cells compromised in double-strand break repair were treated with BPA alone or co-exposed with either potassium bromate (KBrO 3) or laser irradiation as oxidative damaging agents. In experiments with KBrO 3 , co-treatment with BPA partially reversed the KBrO 3-induced cytotoxicity observed in these cells, and this was coincident with an increase in guanine base lesions in genomic DNA. The improvement in cell survival and the increase in oxidatively induced DNA base lesions were reminiscent of previous results with alkyl adenine DNA glycosylase-deficient cells, suggesting that BPA may prevent initiation of repair of oxidized base lesions. With laser irradiation-induced DNA damage, treatment with BPA suppressed DNA repair as revealed by several indicators. These results are consistent with the hypothesis that BPA can induce a suppression of oxidized base lesion DNA repair by the base excision repair pathway.
    PLoS ONE 02/2015; 10(2):e0118819. DOI:10.1371/journal.pone.0118819 · 3.53 Impact Factor
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    ABSTRACT: Oxidative stress mechanisms are involved in hepatotoxicity. The liver is reported to be affected by bisphenol A (BPA) in animals studies, and has been also reported to possess hepatic toxicity. This study aimed to examine association between liver health status and the effects of BPA on the antioxidant defense systems and liver biomarkers. BPA (0, 2, 10, 50 mg/kg) body weight was mixed in corn oil and intra-peritoneally administered every forty-eight hours for 30 days in dose dependent manner. There was no significant difference between the body weight and weight of rat liver in BPA-treated groups and control groups. The study results show that the levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2) increased after exposure to BPA. However, the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were significantly (P<0.001, P<0.05 and P<0.001 respectively) decreased at 50 mg/kg dosage. Liver markers activities such as Lactate dehydrogenase (LDH), Glutamic-oxalacetic transaminase (GOT) and Glutamic-pyruvic transaminase (GPT) were significantly increased, while γ-Glutamyltransferase (γ-GT) activity was decreased. BPA exposure increased activity of liver biomarkers indicating liver hyperactivity. Analysis of the liver section provided essential evidence of liver apoptosis. Moreover, BPA may lead to induced toxic response of liver oxidative system.

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