Influence of repeated liver regeneration on hepatic carcinogenesis by diethylnitrosamine in mice.

In mice given a single dose of diethylnitrosamine, a hepatonecrotic dose of carbon tetrachloride, 5 weeks after dosing with DEN and repeated 6 times at 4-weekly intervals, augmented the tumour yield in the livers. A single hepatonecrotic dose of CCl4 24 h before a single dose of DEN also increased the number of tumours produced. The effect of the repeated administration of CCl4 after the dose of DEN occurred in addition to, and was therefore independent of, the enhancing effect of a single dose of CCl4 before DEN. These results may be interpreted as implying (1) that the liver in the regenerative phase after a hepatonecrotic dose of CCl4 is more susceptible to an initiating action of DEN, i.e. produces more potential foci of tumour growth than in the normal liver and (2) that the repeated doses of CCl4 leading to repeated phases of regeneration, after the dose of DEN, provide a promoting stimulus.