title: Bisphenol a promotes cell survival following oxidative DNA damage in mouse fibroblasts.
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 endogenous 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 excision 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 (KBrO3) or laser irradiation as oxidative damaging agents. In experiments with KBrO3, co-treatment with BPA partially reversed the KBrO3-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.
authors.affiliation: Genomic Integrity and Structural Biology Laboratory, NIEHS, National Institutes of Health, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, United States of America.
authors.forename: Natalie R
authors.initials: NR
authors.lastname: Gassman
authors.affiliation: Biomolecular Measurement Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, United States of America; Faculty of Pharmacy, Gazi University, Ankara, Turkey.
authors.forename: Erdem
authors.initials: E
authors.lastname: Coskun
authors.affiliation: Genomic Integrity and Structural Biology Laboratory, NIEHS, National Institutes of Health, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, United States of America.
authors.forename: Donna F
authors.initials: DF
authors.lastname: Stefanick
authors.affiliation: Genomic Integrity and Structural Biology Laboratory, NIEHS, National Institutes of Health, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, United States of America.
authors.forename: Julie K
authors.initials: JK
authors.lastname: Horton
authors.affiliation: Biomolecular Measurement Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, United States of America.
authors.forename: Pawel
authors.initials: P
authors.lastname: Jaruga
authors.affiliation: Biomolecular Measurement Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, United States of America.
authors.forename: Miral
authors.initials: M
authors.lastname: Dizdaroglu
authors.affiliation: Genomic Integrity and Structural Biology Laboratory, NIEHS, National Institutes of Health, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, United States of America.
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Wilson
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000009:adverse effects*; D001959:Bromates / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D006147:Guanine / Q000378:metabolism*; D028022:Low-Level Light Therapy / Q000009:adverse effects; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000009:adverse effects*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D001959:Bromates; D004247:DNA; D006147:Guanine; D010636:Phenols; C019536:potassium bromate; C006780:bisphenol A; D000098826:Bisphenol A Compounds