Induction of specific monooxygenases by isosteric heterocyclic compounds of benz[ a]anthracene, benzo[ c]phenanthrene and chrysene

Abstract

Benzo[ c]phenanthrene and a series of heterocyclic compounds (benzo[ b]naphtho(1,2- d)thiophene; benzo[ b]naphtho(2,1- d)thiophene; benz[ a]acridine and benz[ c]acridine) were tested for their capacity of inducing monooxygenase activity in rat liver by means of recording the metabolite profile of benz[ a]anthracene formed in rat liver microsomal incubations. Although all compounds tested were found to be weak monooxygenase inducers the pretreatment of rats with them resulted in significant changes of the microsomal metabolite profile of benz[ a]anthracene. The thiophenes equally gave rise to oxidation at the 5,6- and the 8,9-positions, whereas the benzacridines being isosteric to benz[ a]anthracene favoured the K-region oxidation (5,6-oxidation). A structure-dependent effect of monooxygenase inducers on the metabolite profile of benz[ a]anthracene is discussed.