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

A D Ayrton, J Trinick, B P Wood, J N Smith, C Ioannides

Index: Biochem. Pharmacol. 37(23) , 4565-71, (1988)

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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 hydrocarbons markedly increased the O-deethylations of ethoxyresorufin 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-450IAI 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.