title: DNA damage caused by bisphenol A and estradiol through estrogenic activity.
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.
authors.affiliation: GeneCare Research Institute Co. Ltd., 200 Kajiwara, Kamakura, Kanagawa 247-0063, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Iso
authors.forename: Takahide
authors.initials: T
authors.lastname: Watanabe
authors.forename: Teruaki
authors.initials: T
authors.lastname: Iwamoto
authors.forename: Akira
authors.initials: A
authors.lastname: Shimamoto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Furuichi
mesh_terms: D001559:Benzhydryl Compounds; D045744:Cell Line, Tumor; D020552:Comet Assay; D004249:DNA Damage; D052244:Endocrine Disruptors / Q000633:toxicity*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology / Q000633:toxicity*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D006657:Histones / Q000378:metabolism; D006801:Humans; D008856:Microscopy, Fluorescence; D010636:Phenols / Q000633:toxicity*; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D004958:Estradiol; D004965:Estrogen Antagonists; D000077267:Fulvestrant; D006657:Histones; D010636:Phenols; D011960:Receptors, Estrogen; C468783:H2AX protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds