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'-methy-4-dimethylamioazobenzene 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 percent of control values. The decrease of liver weight that occurred in shunted rats without loss of
body weight produced a very 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 has been shown for other microsomal
enzymes.