Effects of various concentrations of ethyl-alpha-p-chlorophenoxyisobutyrate (clofibrate) on diethylnitrosamine-induced hepatic tumorigenesis in the rat.
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 of 0,0.1, 0.25, 0.5, and 1% for 19 weeks. Hepatic tumors greater than 1 mm were counted. The doses of 0.1% and 0.25% clofibrate markedly enchanced the incidence of hepatic tumors, whereas 0.5% clofibrate had no effect and 1% clofibrate markedly inhibited hepatocarcinogenesis. It is clearly 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.
D000818:Animals; D001835:Body Weight; D002994:Clofibrate / Q000009:adverse effects*; D003043:Cocarcinogenesis; D004052:Diethylnitrosamine; D004305:Dose-Response Relationship, Drug; D008113:Liver Neoplasms / Q000139:chemically induced*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008297:Male; D051381:Rats
D004052:Diethylnitrosamine; D002994:Clofibrate