17alpha-Ethinylestradiol hinders nucleotide excision repair in zebrafish liver cells.

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Notch EG, Mayer GD

17alpha-Ethinylestradiol hinders nucleotide excision repair in zebrafish liver cells.

Aquat Toxicol. 2009 Dec 13;95(4):273-8. doi: 10.1016/j.aquatox.2009.01.001. Epub 2009 Jan 23.

PubMed ID

19237207 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Ethinylestradiol	Estrogen receptor alpha	Protein	Humans	Yes	Agonist	Details