Induction of the rat hepatic microsomal mixed-function oxidases by two aza-arenes: A comparison with their non-heterocyclic analogues

Abstract

The ability of the aza-aromatic polycyclic aromatic hydrocarbons 10-azobenz( a)pyrene and benz( a) acridine to induce the rat hepatic microsomal mixed-function oxidases was compared to that of their non-heterocyclic analogues benz( a) pyrene and benz( a) anthracene respectively. All four hydro-carbons markedly increased the O-deethylations of ethoxyresorufln and ethoxycoumarin, the non-heterocyclic analogues being the more potent. A more modest increase was seen in the O-dealkylation of pentoxyresorufin. All four hydrocarbons induced proteins recognised by antibodies to cytochrome P-450aIAI but no increase was seen when antibodies to cytochrome P-450IIB1 were employed. The metabolic activation of benz( a)pyrene and Glu-P-1 to mutagenic intermediates in the Ames test was enhanced by all pretreatments. It is concluded that the aza-aromatic polycyclic hydrocarbons, like their non-heterocyclic analogues, selectively induce the cytochrome P-450I family of proteins.