Dose-response relationship of phenobarbital promotion of diethylnitrosamine initiated tumors in rat liver.
The dose-response relationship was determined in rats for the enhancement by phenobarbital of diethylnitrosamine (DENA)-initiated neoplastic nodules and hepatocellular carcinomas. Male Sprague-Dawley rats received a single oral dose of either 80 mg/kg DENA or water. Seven days later, the animals were divided into groups that started to receive 0, 62.5, 125, 250, 500 or 1000 ppm sodium phenobarbital in the drinking water. Animals from each group were killed at 48 and 70 weeks after the DENA. No significant difference was observed in the low response of neoplastic nodules among the DENA-initiated groups. The incidence of DENA-initiated hepatocellular carcinoma was enhanced at 70 weeks by 250, 500 and 1000 ppm sodium phenobarbital but not by 62.5 or 125 ppm sodium phenobarbital. Equal enhancement of the incidence of hepatocellular carcinomas was obtained with 250, 500 and 1000 ppm sodium phenobarbital. In non-DENA-initiated rats, phenobarbital did not induce neoplastic nodules or hepatocellular carcinomas. Our results suggest that a daily dose of at least 250 ppm sodium phenobarbital is required in order for it to exert tumor promoting activity.
D000818:Animals; D003043:Cocarcinogenesis; D004052:Diethylnitrosamine; D004305:Dose-Response Relationship, Drug; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008297:Male; D009153:Mutagens; D010634:Phenobarbital / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D009153:Mutagens; D004052:Diethylnitrosamine; D010634:Phenobarbital