In vitro metabolism of 4-vinylcyclohexene in rat and mouse liver, lung, and ovary

Toxicology and Applied Pharmacology
D A KellerF A Reitman

Abstract

4-Vinylcyclohexene (4-VCH), the dimer of 1,3-butadiene, is an ovarian toxicant in mice due to the formation of a diepoxide metabolite, but the tissue-specific site of formation of the metabolites is unknown. Microsomal preparations from liver, lung, and ovaries obtained from female Crl:CD BR rats and female B6C3F1 mice were tested for their ability to metabolize the following reactions: 4-VCH to 4-VCH-1,2-epoxide and 4-VCH-7,8-epoxide; 4-VCH-1,2-epoxide to 4-VCH diepoxide and 4-VCH-1,2-diol; 4-VCH-7,8-epoxide to 4-VCH diepoxide and 4-VCH-7,8-diol; and hydrolysis of 4-VCH diepoxide. Microsomes were incubated with the test chemical and the reaction products were analyzed by gas chromatography. Rat liver and lung microsomes and mouse liver and lung microsomes metabolized 4-VCH to 4-VCH-1,2-epoxide at detectable rates. Mouse liver had a Vmax for the reaction that was 56-fold higher than that for rat liver (11.1 and 0.20 nmol/min/mg protein, respectively). The Vmax for mouse lung was 2-fold higher than that for rat lung. 4-VCH-1,2-epoxide formation was not detected in ovarian microsomes from rats or mice. Metabolism of 4-VCH to 4-VCH-7,8-epoxide was detected in microsomes from rat liver and mouse liver and lung, at rates very low co...Continue Reading

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Citations

Jul 16, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Aileen F KeatingPatricia B Hoyer
Jan 24, 2006·Molecular and Cellular Biology·Xiaoming HuQiang Ma
Jul 17, 2001·Drug and Chemical Toxicology·C BevanK S Bentley

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