MODIFICATIONS OF "3'-METHYL-4-DIMETHYLAMINOAZOBENZENE CARCINOGENESIS OF RAT-LIVER AND CARCINOGEN METABOLISM BY PORTACAVAL ANASTOMOSIS

Abstract

The effect of portacaval shunt on hepatocarcinogenesis was studied in rats fed 3''-methyl-4-dimethylaminoazobenzene. Portacaval anastomosis resulted in a decrease of hepatocarcinogenesis as reflected by a delay in the early peak of .alpha.-fetoproteins, an absence of late appearance of .alpha.-fetoproteins and a significantly lower incidence of tumors than in nonshunted rats. Reduction of hepatocarcinogenesis in shunted rats was associated with a decrease of the binding of 3''-methyl-4-dimethylaminoazobenzene metabolites to liver proteins. This effect seemed to be related to modifications of carcinogen-metabolic pathways. While the detoxifying azoreductase activity was not affected by portal diversion, the activating pathway leading to the binding of 4-dimethylaminoazobenzene metabolites to DNA, a major step for cell carcinogenesis that is mediated by microsomal enzymes, was decreased in shunted rats to about 50% of control values. The decrease of liver weight that occurred in shunted rats without loss of body weight produced a significant reduction of the total capacity of liver to activate 4-dimethylaminoazobenzene while the total capacity of detoxification remained unchanged. This could be a direct consequence of portacaval anastomosis, as was shown for other microsomal enzymes.