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

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 the hepatic activity for 3'-Me-DAB metabolism and species difference observed in the carcinogenic activity of the dye were investigated. The hepatic activity for 3'-Me-DAB metabolism with the liver of rats, mice, and hamsters fed a diet containing 3'-Me-DAB was measured by the tracer technique. By the repeated administration of 3'-Me-DAB, the hepatic azo-reduction activity of hamsters was depressed but their N-demethylation activity was conversely promoted throughout the observation period. Consequently, the total conversion of 3'-Me-DAB to metabolites in the liver of hamsters fed the dye remained almost the same as that of the control. In the rat liver, the most sensitive organ for carcinogenesis, 3'-Me-DAB administration had a marked effect on 3'-Me-DAB-metabolizing activity, and the azo-reduction activity was significantly depressed by the feeding of 3'-Me-DAB diet already from 6 hr later throughout the experimental period. In contrast, the N-demethylation reaction of 3'-Me-DAB to 3'-methyl-4-methylaminoazobenzene, a proximate carcinogen, was enhanced in the rat and mouse liver by their treatment only at the early period when the formation of protein-bound dye in the liver rose to a maximum peak by 3'-Me-DAB administration. In the rat hepatic tumors formed by the administration of 3'-Me-DAB for 3-4 months, all the activities for 3'-Me-DAB metabolism were notably decreased. Thus, it was found that the hepatic activities for 3'-Me-DAB metabolism were specifically affected by 3'-Me-DAB administration in all the three species, in which 3'-Me-DAB is carcinogenic or not.