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Modifications of 3'-Methyl-4-dimethylaminoazobenzene Carcinogenesis of Rat Liver and Carcinogen Metabolism by Portacaval Anastomosis¹

Laboratoire de Chirurgie Expérimentale, INSERM U-17 et Université Paris-Sud, Hópital Paul Brousse, 14, avenue Paul Vaillant-Couturier [J-B. R., D. F., J. M., H. B.], and Institut de Recherches Scientifiques sur le Cancer, BP n° 8, [F. D.] 94800 Villejuif, France

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 -fetoproteins, an absence of late appearance of -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-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 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.

¹ This work was supported by Grant 76-5-079-7 from Institut National de la Santé et de la Recherche Médicale and Grant 384 from Faculté de Médecine Paris-Sud.

² To whom requests for reprints should be addressed.

Received 4/ 1/77. Accepted 9/20/77.