Monooxygenase induction by various xenobiotics and its influence on rat liver microsomal metabolism of chrysene in comparison to benz[ a]anthracene

Abstract

The potencies of various xenobiotics for induction of monooxygenases and their influence on the rat liver microsomal metabolite profile of the environmentally relevant weak carcinogen, chrysene, was determined. Among the widely distributed chemicals, polychlorinated biphenyls (PCB) and preferentially 3,3′,4,4′-tetrachlorobiphenyl as well as PAHs and their heterocyclic analogues such as benzo[ a]pyrene, benzo[ b]- and -[ j]fluoranthene, indeno[1,2,3- cd]pyrene, dibenz[ a, h]acridine, benzo[ b]naphtho[2,1- d]thiophene, and 5,6-benzoflavone were found to be potent inducers stimulating the formation of the proximate, and some of them also the ultimate carcinogen of chrysene. Lindane, carbaryl, DDT, and pentachlorophenol were found to be inefficient or weak inducers. With the exception of phenobarbital no inducers were found among the pharmaceuticals investigated. Sex-dependent metabolism was found for Wistar-rats. No 1,2-oxidation was observed in females, and turnover rates were lower than in males. These findings confirm the results previously obtained with benz[ a]anthracene as substrate. The inducing potencies of various compounds tested were similar for both of these substrates. It is interesting to note that in most cases the same effective xenobiotic induces the bay-region diolepoxide in both, chrysene and benz[ a]anthracene.