Dose-dependent enhancing effect of phenobarbital on hepatocarcinogenesis initiated by diethylnitrosamine in the rat.

Sequential feeding of various dose levels of phenobarbital (PB) after diethylnitrosamine (DENA) administration revealed that the enhancing effect of PB on hepatocarcinogenesis was dose-dependent. The highest dose level of PB, 0.2% in the diet, greatly enhanced the formation of tumors larger than 5mm in diameter. Tumors obtained in the 0.2% PB feeding group were more numerous and larger in size than those in th 0.01, 0.05, and 0.1% PB feeding groups. although it took longer, the enhancing effect of 0.01% PB feeding was evident when DENA had been administered for 3 weeks, while the same dose level of PB clearly enhanced hepatocarcinogenesis when the carcinogen had been given for 5 weeks.