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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.
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