The Catalytic Activity of 4 Expressed Human Cytochrome-P450S Towards Benzo[A]Pyrene and the Isomers of its Proximate Carcinogen

The catalytic properties of expressed human cytochromes P4501A1, 1A2, 3A4 and 3A5 with respect to the metabolite distribution for the carcinogen benzo[a]pyrene (BP) and the proximate carcinogen (-)-trans-7,8-dihydroxy- 7,8-dihydrobenzo[a]pyrene ((-)-BP-7,8-DHD) were determined. P4501A1 formed a higher proportion of the proximate carcinogen from BP than the other isozymes. Both P4501A1 and 1A2 were more selective for oxidation at the benzo ring of BP and showed a greater production of dihydrodiol metabolites than either P4503A4 or 3A5. The formation of diolepoxides from the individual enantiomers of BP-7,8-DHD occurred in a highly stereoselective fashion