Article

DNA Damage Caused by Bisphenol A and Estradiol through Estrogenic Activity

St. Marianna University School of Medicine, Kawasaki Si, Kanagawa, Japan
Biological & Pharmaceutical Bulletin (Impact Factor: 1.83). 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.

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Available from: Akira Shimamoto, Jan 06, 2014
    • "Moreover, its range of toxicity is relatively high as a result of their multiples effects on reproduction, metabolism or obesity development (Kang et al., 2002) being those involving the cardiovascular system one of the main health concerns. Direct exposure to BPA (or gestational exposure in mammals) has been reported to cause epigenetic effects (Miao et al., 2014; Singh and Li, 2012; Corrales et al., 2014) and DNA fragmentation (Iso et al., 2006). Therefore, its effects on reproductive health could go beyond the decrease in the production of spermatozoa since changes affecting the germline could be transmitted transgenerationally to subsequent generations (Manikkam et al., 2013; Lam et al., 2011). "
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    ABSTRACT: Bisphenol A (BPA) is an endocrine disruptor used in manufacturing of plastic devices, resulting in an ubiquitous presence in the environment linked to human infertility, obesity or cardiovascular diseases. Both transcriptome and epigenome modifications lie behind these disorders that might be inherited transgenerationally when affecting germline. To assess potential effects of paternal exposure on offspring development, adult zebrafish males were exposed to BPA during spermatogenesis and mated with non-treated females. Results showed an increase in the rate of heart failures of progeny up to the F2, as well as downregulation of 5 genes involved in cardiac development in F1 embryos. Moreover, BPA causes a decrease in F0 and F1 sperm remnant mRNAs related to early development. Results reveal a paternal inheritance of changes in the insulin signaling pathway due to downregulation of insulin receptor β mRNAs, suggesting a link between BPA male exposure and disruption of cardiogenesis in forthcoming generations. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · Aug 2015 · Environmental Pollution
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    • "ROS are scavenged by the endogenous antioxidant defense system, including superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH-Px) in cells. The phenolic compound such as BPA is known to cause abnormalities, DNA damage, and genotoxicity [14] in the liver of rats and mice [3]. Therefore, it has been established that the early environmental stress during developmental stages could cause persistent changes in mitochondrial activity of nonhuman primates [15], which highlights the influence of early exposure for development of disease later in life. "
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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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    • "A few studies with cellular models indicated that BPA has the potential to induce point mutation, double stranded DNA breaks, and aneuploidy (57, 58; Table 2). Human studies of BPA exposure and sperm DNA damage have been very limited. "
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    ABSTRACT: Endocrine disrupting chemicals (EDCs) can interfere with normal hormonal balance and may exert adverse consequences on humans. The male reproductive system may be susceptible to the effects of such environmental toxicants. This review discusses the recent progress in scientific data mainly from epidemiology studies on the associations between EDCs and male reproductive health and our understanding of possible mechanisms associated with the effects of EDCs on male reproductive health. Finally, the review provides recommendations on future research to enhance our understanding of EDCs and male reproductive health. The review highlights the need for (1) well-defined longitudinal epidemiology studies, with appropriately designed exposure assessment to determine potential causal relationships; (2) chemical and biochemical approaches aimed at a better understanding of the mechanism of action of xenoestrogens with regard to low-dose effects, and assessment of identify genetic susceptibility factors associated with the risk of adverse effects following exposure to EDCs.
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