Biological activity of benzo[e]pyrene. An assessment based on mutagenic activities and metabolic profiles of the polycyclic hydrocarbon and its derivatives.

The potential biological activity of benze(e)pyrene was investigated by a determination of the mutagenic activity of the polycyclic hydrocarbon and six of its derivatives in the absence and presence of a cytochrome P-450-dependent monooxygenase system. In the presence of hepatic microsomes from Aroclor 1254-pretreated rats or the cytochrome P-450-dependent monooxygenase system purified to near homogeneity from these microsomes, benzo(e)pyrene, and trans-9,10-dihydroxy-9,10,11,12-tetrahydrobenzo(e)pyrene were metabolized to products which had little or no mutagenic activity toward Salmonella typhimurium. Under the same assay conditions, the products formed from trans-4,5-dihydroxy-4,5-dihydrobenzo(e)pyrene had modest mutagenic activity. In contrast with these results, 9,10-dihydrobenzo(e)pyrene was metabolically activated to potent mutagenic products which were more active than the products formed from benzo(e)pyrene. The high intrinsic mutagenic activity of the chemically synthesized beings ring tetrahy-drospoxide of 9,10-dihydrobenzo(e)pyrene after metabolism was mediated by this bay region tetrahydroepoxide. Lack of formation of a benzo ring epoxide provides a rationale for the inability of 9,10-dihydroxy-9,10-dihydrobenzo(e)pyrene to be metabolically activated by rat liver enzymes to mutagenic products and may contribute to the low carcinogenic activity of benzo(e)pyrene in rodents.