PUBLICATION
17alpha-Ethinylestradiol hinders nucleotide excision repair in zebrafish liver cells
- Authors
- Notch, E.G., and Mayer, G.D.
- ID
- ZDB-PUB-090302-19
- Date
- 2009
- Source
- Aquatic toxicology (Amsterdam, Netherlands) 95(4): 273-278 (Journal)
- Registered Authors
- Keywords
- Ethinylestradiol, Zebrafish, Nucleotide excision repair, XPA, XPC, ICI 182,780
- MeSH Terms
-
- Animals
- DNA Repair/drug effects*
- Estradiol/analogs & derivatives
- Estradiol/pharmacology
- Estrogen Antagonists/pharmacology
- Estrogens/toxicity*
- Ethinyl Estradiol/toxicity*
- Liver/drug effects*
- Liver/metabolism
- RNA, Messenger/metabolism
- Zebrafish/metabolism*
- PubMed
- 19237207 Full text @ Aquat. Toxicol.
Citation
Notch, E.G., and Mayer, G.D. (2009) 17alpha-Ethinylestradiol hinders nucleotide excision repair in zebrafish liver cells. Aquatic toxicology (Amsterdam, Netherlands). 95(4):273-278.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping