Hepatic Bioactivation of 4-Vinylcyclohexene to Ovotoxic Epoxides
4-Vinylcyclohexene (VCH) is produced by a dimerization reaction of 1,3-butadiene (Rappaport and Fraser, 1976). The curing process of synthetic rubber production results in butadiene dimerization, discharge of VCH, and subsequent exposure of workers to VCH by inhalation (Rappaport and Fraser, 1977). Chronic exposure of humans to VCH may be of concern since a 2 yr bioassay indicated that VCH was carcinogenic to mice (Collins et al., 1987). Chronic gavage of female B6C3F1 mice caused the induction of rare ovarian tumors. These tumors were not observed in VCH-treated Fischer 344 rats (NTP, 1986). Studies in our laboratory have centered on determining the basis for the species difference in VCH-induced ovarian toxicity. Such studies have provided information which may aid in determining which species best predicts the response of humans exposed to VCH. In addition, clues have been obtained pertaining to the mechanism by which VCH produces ovarian injury.
KeywordsReactive Intermediate Epoxide Hydrolase Hepatic Microsome P4S0 Form National Toxicology Program
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- Jull, J.W. (1973). Ovarian tumorigenesis. Methods Cancer Res. 7, 131–186.Google Scholar
- National Toxicology Program (1986). Toxicology and carcinogenesis studies of 4vinylcyclohexene in F344/N rats and B6C3F1 mice. NTP technical report no 303. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Public Information, National Toxicology Program, P.O. box 12333, Research Triangle Park, N.C.Google Scholar
- Sipes, I.G. and Gandolfi, A.J. (1986). Biotransformation of toxicants. In Toxicology. The Basic Science of Poisons ( Klaassen, C., Amdur, M., and Doull, J. eds.), pp. 64–98, New York, NY.Google Scholar
- Smith, B.J., Mattison, D.R., and Sipes, I.G. (1990a). The role of epoxidation in 4-vinylcyclohexene-induced ovarian toxicity. Toxicol. Appl. Pharmacol., manuscript submitted.Google Scholar
- Smith, B.J., Carter, D.E., and Sipes, I.G. (1990b). The disposition and in vitro metabolism of 4-vinylcyclohexene in the female mouse and rat. Toxicol. Appl. Pharmacol., manuscript submitted.Google Scholar
- Smith, B.J., Sipes, I.G., Stevens, J.C., and Halpert, J.R. (1990c). The biochemical basis for the species difference in hepatic microsomal 4-vinylcyclohexene epoxidation between female mice and rats. Carcinogenesis, manuscript submitted.Google Scholar