Nutrition and enzyme inducers in liver tumor promotion in human and rat.

Phenobarbital and other substances that cause induction of P450 linked enzymes in the liver are potent tumour promoters when given to rats after a single dose of dimethyl or diethyl nitrosamine. The human population is known to be exposed to small amounts of nitrosamines and to inducers of P450 linked enzymes in the liver, from natural foods such as cabbage and other brassicas. Many individuals are exposed to induced doses of phenobarbital used as anti convulsants. Cohort studies have shown that there is no increased risk of liver cancer detectable in people taking phenobarbital who suffer from epilepsy. On investigating the dose response curve for tumour promotion one finds that hepatocellular carcinomas only appear at a high dosage of phenobarbital and it seems likely that the human exposure to inducers in food, and in therapy with anticonvulsants, is in the dosage range well below that which causes promotion of liver cancer. The physiological adaptation to environment must be clearly distinguished from the pathological events which take place in experimental overdose.