title: 17alpha-Ethinylestradiol hinders nucleotide excision repair in zebrafish liver cells.
abstract: Nucleotide excision repair (NER) is the primary mechanism that removes bulky DNA adducts such as those caused by ubiquitous environmental mutagens including benzo(a)pyrene and other polycyclic aromatic hydrocarbons. Recent data suggest that exposure to environmentally relevant concentrations of estrogen decreases hepatic mRNA abundance of several key NER genes in adult zebrafish (Danio rerio). However, the impact of decreased hepatic NER expression on NER function was not investigated in the previous study. The goal of this study was to examine the effect of the potent estrogen receptor agonist 17alpha-ethinylestradiol (EE(2)) on rate and magnitude of bulky DNA adduct repair. Here we show that exposure of zebrafish liver (ZFL) cells to physiologically relevant concentrations of EE(2) resulted in reduced ability of ZFL cells to repair damaged DNA in comparison to control cells. Co-exposure to EE(2) and a complete estrogen receptor antagonist (ICI 182,780) also resulted in reduced NER capacity, whereas ICI 182,780 alone did not affect the ability of ZFL cells to repair UV damage. These results indicate that estrogen exposure can decrease cellular NER capacity and that this effect can occur in the presence of an estrogen receptor antagonist, suggesting that EE(2) can affect NER processes through mechanisms other than nuclear estrogen receptor activation.
authors.affiliation: Department of Biochemistry, Microbiology and Molecular Biology, University of Maine 5735 Hitchner Hall, Orono, ME 04469, USA.
authors.forename: Emily G
authors.initials: EG
authors.lastname: Notch
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Mayer
mesh_terms: D000818:Animals; D004260:DNA Repair / Q000187:drug effects*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000633:toxicity*; D004997:Ethinyl Estradiol / Q000633:toxicity*; D000077267:Fulvestrant; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015027:Zebrafish / Q000378:metabolism*
chemical_list: D004965:Estrogen Antagonists; D004967:Estrogens; D012333:RNA, Messenger; D000077267:Fulvestrant; D004997:Ethinyl Estradiol; D004958:Estradiol