Bisphenol a promotes cell survival following oxidative DNA damage in mouse fibroblasts

• Published in: PloS one Vol. 10; no. 2; p. e0118819
• Main Authors: Gassman, Natalie R, Coskun, Erdem, Stefanick, Donna F, Horton, Julie K, Jaruga, Pawel, Dizdaroglu, Miral, Wilson, Samuel H
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.02.2015; Public Library of Science (PLoS)
• Subjects: Adenine; Animals; Base excision repair; Benzhydryl Compounds - adverse effects; Biological activity; Biology; Bisphenol A; Bromates - pharmacology; Cancer; Cell cycle; Cell Line; Cell survival; Cell Survival - drug effects; Consumer products; Cytotoxicity; Deoxyribonucleic acid; Diabetes mellitus; DNA; DNA - drug effects; DNA - radiation effects; DNA damage; DNA Damage - drug effects; DNA glycosylase; DNA methylation; DNA polymerase; DNA repair; DNA Repair - drug effects; DNA Repair - radiation effects; Double-strand break repair; Enzymes; Exposure; Fibroblasts; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - radiation effects; Gene expression; Genomes; Genomics; Guanine; Guanine - metabolism; Impact damage; Irradiation; Laboratories; Laser damage; Lasers; Lesions; Low-Level Light Therapy - adverse effects; Mice; Obesity; Oxidative stress; Oxidative Stress - drug effects; Oxygen; Phenols; Phenols (Class of compounds); Phenols - adverse effects; Potassium; Potassium bromate; Purines; Radiation damage; Reactive oxygen species; Repair; Reproductive disorders; Survival; Toxicity; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0118819

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.