Sequential analysis of hepatic carcinogenesis. Regeneration of liver after carbon tetrachloride-induced liver necrosis when hepatocyte proliferation is inhibited by 2-acetylaminofluorene.

The effect of inhibition of hepatocyte proliferation by dietary 2-acetylaminofluorene (2-AAF) on the restoration of liver in rats after a necrogenic dose of carbon tetrachloride has been studied. The liver weights remained low during the entire feeding period of the 2-AAF, and virtually no hepatocyte proliferation was seen, as determined autoradiographically after thymidine incorporation and by the absence of mitotic figures. Oval cell proliferation was extensive. Morphometric analysis showed (a) equal and maximum liver cell necrosis by 24 hours in both the experimental and control groups, (b) similar kinetics of removal of dead liver cells, and (c) similar values for the mean liver cell area. The distance between the portal triad and terminal hepatic vein in animals on the dietary 2-AAF was considerably reduced. Massive hepatocyte proliferation began after termination of the 2-AAF diet, and the liver returned to normal appearance within 14 days. The oval cells disappeared during this period of liver cell restoration. A new hypothesis for oval cell proliferation based on differential inhibition of hepatocyte proliferation resulting in unbalanced growth of ductular cells is presented.