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Effect of dietary phenobarbital on the development of enzyme-altered islands (EAI) and hepatocellular carcinomas initiated by a short-term treatment with 3'-methyl-4-(dimethylamino) azobenzene (3'-Me-DAB) or diethylnitrosamine (DENA) in the rat was studied. Phenobarbital generally enhanced the proliferation of carcinogen-induced (enzyme-altered) cells so that the number and size of EAI were much larger in phenobarbital-fed groups in early stages than in control groups kept on a basal diet. The growth rate of EAI was, however, not uniform and only a small minority progressed to large islands or carcinomas. In groups initially treated with 3'-Me-DAB for 3 weeks, the enhancing effect of phenobarbital on cancer production was remarkable by the 36th week whereas in groups treated with 3'-Me-DAB for 1 week, no cancer developed by the 60th week, although a large number of small EAI appeared. Thus a summation effect of the carcinogen was observed even when the carcinogen was given for a short period as an initiator. The enhancing effect of phenobarbital was also marked in the groups initiated by DENA, in which, however, considerable number of carcinomas developed in control groups also. The carcinogen-induced cells or EAI appeared inherently different, as the population, in the potentiality to progress to carcinoma according to the difference of an initiator.

Enhancing effect of phenobarbital on the development of enzyme-altered islands and hepatocellular carcinomas initiated by 3'-methyl-4-(dimethylamino) azobenzene or diethylnitrosamine.