Effects of various concentrations of ethyl-α-p-chlorophenoxyisobutyrate (clofibrate) on diethylnitrosamine-induced hepatic tumorigenesis in the rat

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Abstract
Male F344 rats were given diethylnitrosamine in drinking water at a concentration of 40 p.p.m. for 5 weeks. One week later, the rats were fed diet containing clofibrate at concentrations of 0, 0.1, 0.25, 0.5, and 1% for 19 weeks. Hepatic tumors > 1 mm were counted. The doses of 0.1% and 0.25% clofibrate markedly enhanced the incidence of hepatic tumors, whereas 0.5% clofibrate had no effect and 1% clofibrate markedly inhibited hepatocarcinogenesis. It is dearly demonstrated in the present experiments that the lower doses of clofibrate (0.1% and 0.25%) promote hepatocarcinogenesis. The higher doses of clofibrate (0.5% and 1%) depress weight gain by lowering the intake of food. This lowered food intake might contribute to inhibition of hepatocarcinogenesis.