Lack of effect of phenobarbital on hepatocellular carcinogenesis initiated by N-nitrosodiethylamine or methylazoxymethanol acetate in male Syrian golden hamsters.

Subchronic toxicity and long-term tumor-promoting effects of phenobarbital (PB) were investigated in male Syrian golden hamsters. In subchronic studies, PB was administered in drinking water to 5-week-old male hamsters for periods of 8 or 16 weeks at dosage levels of 250, 500, or 1000 ppm. No significant change in the ratio of liver weight to body weight was observed at 8 weeks; however, at 16 weeks there was a dose-dependent increase in the ratio of liver weight to body weight and a significant decrease in body weight gain among animals that received PB at 1000 ppm. The effect of PB on hepatic cytochrome P-450 and P-450-dependent aminopyrine N-demethylase activity was compared in male Syrian golden hamsters, F-344/NCr rats, and B6C3F1 mice. PB enhanced cytochrome P-450 activity in all three species; however, a significant increase (p less than 0.05) in aminopyrine N-demethylase activity was observed only in rats and mice. Potentially preneoplastic hepatocellular hyperplastic foci and hepatocellular neoplasms were studied in weanling male Syrian golden hamsters that received a single ip injection of either 100 mg N-nitrosodiethylamine (DEN)/kg body wt or 20 mg methylazoxymethanol acetate (MAM)/kg body wt at 5 weeks of age, followed by administration of 500 ppm PB in drinking water that began 2 weeks after the carcinogen injection and continued to 69 weeks of age. Groups of hamsters were killed at 25, 52, and 69 weeks of age; portions of liver and other organs with gross lesions were fixed in Formalin and examined histologically. MAM was a more potent hepatocarcinogen than DEN in male Syrian golden hamsters. PB failed to promote the development of either preneoplastic hepatocellular foci or hepatocellular neoplasms (adenomas or carcinomas) in either DEN- or MAM-initiated hamsters. Also, PB had no effect on the development of nonhepatic lesions occurring either spontaneously or induced by DEN or MAM in these animals.