The influence of cytochrome P-450 induction on the disposition of carcinogenic benzo[a]pyrene 7,8-dihydrodiol 9,10-epoxide in isolated cells.

The disposition of the carcinogenic (+)-7 beta, 8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE] has been studied in isolated hepatocytes obtained from 3-methylcholanthrene-pretreated rats. In these cells different routes are acting in concert and contribute to diol-epoxide elimination. Conjugation of (+)-anti-BPDE with glutathione (GSH) and cytochrome P-450c-mediated metabolism of the diol-epoxide to 1- and 3-hydroxy-anti-BPDE (triol-epoxides) appears to be equally important. The reactive triol-epoxides undergo a number of secondary reactions, including covalent binding to cellular constituents, e.g. protein and GSH, and hydrolysis to pentahydroxyderivatives. The effective intracellular lifetime of (+)-anti-BPDE is approximately 1 min and comparable to that previously observed in hepatocytes obtained from uninduced animals.