CHEMICAL CARCINOGENESIS AND CYTOCHROME-P4 50 - CARCINOGENIC AROMATIC AMINE-INDUCED P450 AND HEPATOCARCINOGENIC SUSCEPTIBILITY TO THE AROMATIC AMINE IN THE RODENT

The N-hydroxyl and/or N-acetoxy derivatives of carcinogenic Q-aminoazo dyes, which were thought to be proximate and ultimate metabolites, we re synthesized in our laboratory in 1975, and their chemical and biolo gical characteristics were further examined. The results strongly supp orted the hypothesis that the metabolic conversions, N-hydroxylation a nd its O-acylation, of carcinogenic aromatic amines are important proc esses for their carcinogenicity. Carcinogenic aromatic amines such as heterocyclic aromatic amines and aminoazo dyes induced predominantly c ytochrome P450IA2 (CYP1A2), which is responsible for the mutagenic act ivation and N-hydroxylation of the amines in the rodent. The induction rate and total activity of this enzyme were well correlated with sex, species, and target organ differences in hepatocarcinogenic susceptib ility of animals to the aromatic amines. During hepatocarcinogenic pro cess with an aromatic amine, the expression and induction of CP1A2 dec reased especially in preneoplastic liver cells as judged by the expres sion of a placental form of glutathione 5-transferase.