CHEMICAL CARCINOGENESIS AND CYTOCHROME-P4 50 - CARCINOGENIC AROMATIC AMINE-INDUCED P450 AND HEPATOCARCINOGENIC SUSCEPTIBILITY TO THE AROMATIC AMINE IN THE RODENT
M. Degawa, CHEMICAL CARCINOGENESIS AND CYTOCHROME-P4 50 - CARCINOGENIC AROMATIC AMINE-INDUCED P450 AND HEPATOCARCINOGENIC SUSCEPTIBILITY TO THE AROMATIC AMINE IN THE RODENT, Yakugaku zasshi, 115(1), 1995, pp. 1-14
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.