Protective value of a liver initiation-promotion regimen against the lethal effect of carbon tetrachloride in rats.

This study was designed as one test of the hypothesis that an early sequence of steps in hepatocarcinogenesis in the rat, with the production of hepatocyte nodules, may be a special form of adaptive response that has survival value for the host. Fischer 344 rats were initiated with a single dose of diethylnitrosamine. Hepatocyte nodules were rapidly generated by selecting for resistant hepatocytes by a brief exposure to 2-acetylaminofluorene coupled with partial hepatectomy, a procedure that leads to liver cancer without any further treatment. Most animals with hepatocyte nodules were completely resistant to single doses of CCl4 that induced 100% mortality in control animals. The demonstration of this protective effect is consistent with the proposed hypothesis.