Modification of N-nitrosobis (2-hydroxypropyl) amine-induced carcinogenesis by orally administered clofibrate in hamsters

Clofibrate, one of hypolipidemic compounds, has been shown as a hepatocarcinogen in rats. In the present experiment, effects of clofibrate given in the promotion stage on liver, gallbladder, pancreas, lung, and kidney carcinogenesis were investigated in male Syrian golden hamsters. After subcutaneous administration of BHP at a dose of 500 mg/kg body weight once a week for 5 weeks, hamsters were maintained on diet containing 0.25% or 0.5% clofibrate for 30 weeks. The hepato-promoting activity of clofibrate was indicated by multiplicity of liver lesions including hyperplastic nodules and hepatocellular carcinomas and it was greater in hamsters given 0.25% clofibrate than in those receiving 0.5% clofibrate. Peroxisome proliferation was observed in the hepatocytes of hamster given 0.5% clofibrate for 13 weeks under the electron microscope. Inhibitry effect of clofibrate was demonstrated in the development of pancreatic duct adenocarcinoma and lung neoplasms, including adenoma and adenocarcinoma. Hypolipidemic status shown in the serum of hamsters given clofibrate might be involved in the inhibitory effect on pancreas and lung carcinogenesis. Clofibrate did not affect gall bladder and kidney carcinogencsis. These results indicated that clofibrate modulated liver, pancreas, and lung carcinogenesis in hamsters.