Activation of benzo(a)pyrene-7,8-dihydrodiol in rat uterus: an in vitro study

Peroxidatic metabolism of benzo(a)pyrene-7,8-dihydrodiol by calcium containing extracts of rat uteri was investigated. Covalently bound and soluble metabolites of benzo(a)pyrene-7,8-dihydrodiol were quantitated by radiometry and high performance liquid chromatography, respectively. 1. Uterine extracts incubated with benzo(a)pyrene-7,8-dihydrodiol activated this proximate mutagen to protein binding metabolite(s). 2. Hydrogen peroxide increased the protein binding and yielded a substantial amount of benzo(a)pyrene-trans-anti-tetrahydrotetrol, suggesting the peroxyl-type free-radical epoxidation process. 3. The results indicate that rat uterine peroxidase is able to catalyze free-radical activation of benzo(a)pyrene-7,8-dihydrodiol by epoxidation to its 9,10-dihydrodiolepoxide, a known ultimate mutagen and carcinogen.