Modulation of N-nitrosobis(2-hydroxypropyl)amine-induced carcinogenesis by clofibrate in hamsters

The effects of clofibrate treatment on N-nitrosobis(2-hydroxypropyl)amine (BHP) induced liver, gall bladder, pancreas, lung and kidney carcinogenesis in hamsters were studied. Animals were given BHP as an initiator at a dose of 500 mg/kg body weight subcutaneously once a week for 5 weeks followed by diet containing 0.25 or 0.5% clofibrate for 30 weeks. Both doses of clofibrate promoted hepatocarcinogenesis as judged from the associated multiplicity of liver lesions including hyperplastic nodules and hepatocellular carcinomas. gamma-Glutamyltranspeptidase (gamma-GTP) activity was not expressed in those lesions in the liver of hamsters given BHP followed by a basal diet or diets containing clofibrate. Clofibrate at a dose of 0.5% in the diet, in contrast, inhibited the development of pancreatic adenocarcinomas and lung neoplasms, including adenomas and adenocarcinomas, without affecting carcinogenesis in the gall bladder and kidney. These results clearly indicate differential modification potential of clofibrate for BHP-induced liver, pancreas and lung carcinogenesis in Syrian hamsters.