Species Differences in DNA Damage by Butadiene: Role of Diepoxybutane
In microsomal incubates 1,3-butadiene (BD) is metabolized by cytochrome P- 450 to its epoxide 1,2-epoxybutene (EB). Further metabolic transformation of the epoxide intermediate by epoxide hydrolase and/or monoxygenase would lead to 3,4-epoxy-1,2-butanediol (via 3-butene-l,2-diol) and to diepoxybutane (DEB, Malvoisin and Roberfroid 1982; Laib et al 1988). Remarkable species differences in the carcinogenic potency of BD between rats (Sprague-Dawley) and mice (B6C3F1) have been demonstrated (Huff et al 1985). The increased susceptibility of mice to BD-induced carcinogenesis has been attributed to the higher metabolic rate of BD, limited detoxification of EB and to the resulting accumulation of reactive epoxide intermediates in this species (Kreiling et al 1987; Laib et al 1988). To investigate comparatively the role of EB and DEB in BD-induced carcinogenesis in both species, studies on alkylation and alkaline filter elution of DNA were carried out in mice and rats.
KeywordsEpoxide Hydrolase High Metabolic Rate Guanine Residue Carcinogenic Potency Alkaline Elution
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