Formation of dihydrodiol metabolites of benzo(alpha)pyrene in cultured human and murine skin cells.
The formation of the 7, 8-a and 9, 10-dihydrodiol metabolites of benzo(a)pyrene, which are believed to play a role in the chemical induction of tumors, was investigated in cultures of human and murine origin. It was found that cultures of mouse (strain C3Hz) epidermal and skin fibroblastic cells showed inducible benzo(a)pyrene metabolism towards dihydrodiol metabolites, after pre-incubation with benz(a)anthracene. This was consistent with the increased in vivo formation of dihydrodiol metabolites of benzo(a)pyrene after injection with 3-methylcholanthrene. In contrast, in human cell cultures the metabolism of benzo(a)pyrene to the dihydrodiol metabolites was not enhanced after pre-exposure to benz(a)anthracene. This was the case in low-passage skin fibroblasts, primary epidermal skin cells, and primary keratinocytes from hair follicles. Moreover, other inducers of microsomal oxygenases, such as phenobarbital and 3-methylcholanthrene, were also unable to increase benzo(a)pyrene metabolism towards the dihydrodiol compounds. In view of these results, obtained using in vitro human and murine model systems, we may conclude that human and murine skin cell culture systems respond differently to pre-treatment with inducers of microsomal monooxygenases with respect to the metabolism of benzo(a)pyrene to reactive dihydrodiol metabolites. The possible implications for the human in vivo situation are discussed.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D001345:Autoradiography; D001580:Benzopyrenes / Q000378:metabolism*; D002478:Cells, Cultured; D004101:Dihydroxydihydrobenzopyrenes; D004790:Enzyme Induction / Q000187:drug effects; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008748:Methylcholanthrene; D051379:Mice; D008815:Mice, Inbred Strains; D012867:Skin / Q000166:cytology / Q000378:metabolism
D001580:Benzopyrenes; D004101:Dihydroxydihydrobenzopyrenes; C017228:benzo(a)pyrene 7,8-dihydrodiol; C020738:9,10-dihydro-9,10-dihydroxybenzo(a)pyrene; D008748:Methylcholanthrene; D001189:Aryl Hydrocarbon Hydroxylases