Effect of simultaneous administration of clofibrate with diethylnitrosamine on hepatic tumorigenesis in the rat.

Effect of clofibrate administered simultaneously with diethylnitrosamine (DEN) on hepatocarcinogenesis in F344 male rats was investigated. DEN was given in drinking water at a concentration of 40 ppm for 5 weeks. Rats were fed the diet containing clofibrate at concentrations of 0.1% and 0.25% during DEN-treatment. All rats were killed 25 weeks after the beginning of DEN-treatment, and hepatic tumors over 1 mm in diameter were counted. Hepatic tumors in the rats given clofibrate at both concentrations were twice as many as those in rats given DEN alone. The significant increase in number of hepatic tumors was observed mainly in the tumors under 10 mm in diameter. Thus, the enhancing effect of clofibrate on hepatocarcinogenesis was evident even when fed simultaneously with the carcinogen, in contrast with phenobarbital (PB).