Studies on carcinogenic azo dyes. VII. Changes in the hepatic activities of 3'-Me-DAB metabolism by rat, mouse, and hamster during the repeated administration of 3'-Me-DAB.

Abstract

The metabolic pattern of 3''-methyl-4-dimethylaminoazobenzene (3''-Me-DAB) in the rat liver through the course of hepatic carcinogenesis by 3''-Me-DAB and the relationship between hepatic 3''-Me-DAB metabolism and species difference observed in the carcinogenic activity of the dye were investigated. Hepatic 3''-Me-DAB metabolism in rats, mice and hamsters fed a diet containing 3''-Me-DAB was measured by the tracer technique. By repeated administration of 3''-Me-DAB, hepatic azo reduction in hamsters was depressed but N-demethylation activity was promoted throughout the observation period. The total conversion of 3''-Me-DAB to metabolites in the liver of hamsters fed the dye remained almost the same as that of controls. In rat liver, the most sensitive organ for carcinogenesis, 3''-Me-DAB administration had a marked effect on 3''-Me-DAB metabolizing activity, and azo reduction was significantly depressed by feeding the 3''-Me-DAB diet from 6 h later throughout the experimental period. N-demethylation of 3''-Me-DAB to 3''-methyl-4-methylaminoazobenzene, a proximate carcinogen, was enhanced in rat and mouse liver by treatment only in the early period when the formation of protein-bound dye in the liver rose to a maximum peak by 3''-Me-DAB administration. In rat hepatic tumors formed by administration of 3''-Me-DAB for 3-4 mo., all activities of 3''-Me-DAB metabolism were notably decreased. Hepatic 3''-Me-DAB metabolism was specifically affected by 3''-Me-DAB administration in all 3 spp., in which 3''-Me-DAB was carcinogenic or not.