INDUCTION OF CYTOCHROME-P450 ISOFORMS BY CARCINOGENIC AROMATIC-AMINESAND CARCINOGENIC SUSCEPTIBILITY OF RODENT ANIMALS

Hepatocarcinogenic aromatic amines such as 4-aminoazobenzene derivativ es and heterocyclic aromatic amines of cooked food origin were found t o be liver-selective cytochrome P450IAZ (CYP1A2) inducers. Each aromat ic amine showed different species-specificity among rodent experimenta l animals in terms of the extent of P450 induction. Carcinogenic susce ptibility of an animal to the amine was well correlated with the activ ity and/or inducibility of CYP1A2 in the animals in the early initiati on phase of the carcinogenesis. In hyperplastic nodules of rat liver, expression and induction of CYP1A2 as suppressed, especially in the pl acental form of glutathione S-transferase-positive foci, Despite the d ecrease of P450s including CYP1A2 in the rat liver bearing hyperplasti c nodules, DNA adducts formed by a carcinogenic aromatic amine increas ed, as compared to the controls, suggesting that the activity of DNA r epair enzyme(s) for the amine-derived DNA adducts might decrease in th e hyperplastic nodules of rat liver. Treatment of rats with lead nitra te revealed a pattern of P450 expression in the liver similar to that observed with rats bearing hyperplastic nodules. These findings may pr ovide valuable information on the roles of P450s in carcinogenic susce ptibility of animals to aromatic amines and in the carcinogenic proces s.