CARCINOGENICITY IN THE HAMSTER OF SIMULTANEOUSLY ADMINISTERED 2-ACETAMIDOFLUORENE AND 3-METHYLCHOLANTHRENE

Abstract

The comparative carcinogenicities of 2-acetamidofluorene, 3-methylcholanthrene, and 2-acetamidofluorene plus 3-methylcholanthrene in the hamster were investigated. Unlike the case with rats, no inhibition of tumor induction was observed when 3-methylcholanthrene was fed to hamsters simultaneously with 2-acetamidofluorene. Combined feeding of 2-acetamidofluorene and 3-methylcholanthrene resulted in adenocarcinoma of the intrahepatic bile ducts, pancreatic adenocarcinoma, and mesenterial sarcomas, while benign cystadenomas of the intrahepatic bile ducts were the only tumors observed in the hamsters fed 2-acetamidofluorene alone. Analyses for urinary metabolites of 2-acetamidofluorene revealed relatively little effect of 3-methylcholanthrene when fed simultaneously with 2-acetamidofluorene. Likewise, the continuous administration of 3-methylcholanthrene in the diet simultaneously with 2-acetamidofluorene caused no increase in the hepatic Nhydroxylation activity in vitro as compared to that of hamsters fed only one of these compounds. One possible explanation of the synergistic action of the combined feeding of 2-acetamidofluorene and 3-methylcholanthrene in producing tumors in extrahepatic tissues is that dietary 3-methylcholanthrene enhances the N-hydroxylation of 2-acetamidofluorene in these tissues.