Title: Effect of arsenite on the induction of CYP1A4 and CYP1A5 in cultured chick embryo hepatocytes.
Authors: Jacobs, J M; Nichols, C; Marek, D; Gorman, N; Walton, H S; Sinclair, P R; Sinclair, J F
Published In Toxicol Appl Pharmacol, (2000 Nov 1)
Abstract: We had reported previously that 2.5-5 microM sodium arsenite decreased the phenobarbital-mediated induction of CYP2H activity and protein but not CYP2H1 mRNA in chick-embryo hepatocyte cultures. Induction of a CYP1A activity and protein by 3-methylcholanthrene was also decreased by low arsenite concentrations; however, CYP1A mRNAs were not measured in those studies. We report here that low concentrations of arsenite decreased induction of activities and mRNAs of two chicken cytochromes P450, CYP1A (1A4 and 1A5), by 3-methylcholanthrene in chick-embryo hepatocyte cultures. Arsenite treatment did not affect the turnover of either mRNA, nor did it decrease the superinduction of each mRNA caused by treatment with cycloheximide in addition to 3-methylcholanthrene. Glutathione depletion enhanced the effect of arsenite to decrease induction of CYP1A4. These results indicate the induction of CYP1A4 and 1A5 is inhibited by sodium arsenite at the level of transcription, suggesting that the Ah receptor complex may be involved.
PubMed ID: 11042089
MeSH Terms: Animals; Arsenites/toxicity*; Aryl Hydrocarbon Hydroxylases*; Avian Proteins*; Cells, Cultured; Chick Embryo; Cycloheximide/pharmacology; Cytochrome P-450 Enzyme System/biosynthesis*; Cytochrome P-450 Enzyme System/metabolism; Enzyme Induction/drug effects; Glutathione/physiology; Hepatocytes/drug effects; Hepatocytes/enzymology*; Indicators and Reagents; Microsomes, Liver/drug effects; Microsomes, Liver/enzymology; Oxidation-Reduction; Oxidoreductases/biosynthesis*; Oxidoreductases/metabolism; Protein Synthesis Inhibitors/pharmacology; RNA, Messenger/biosynthesis; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.; Uroporphyrinogens/biosynthesis