An origin of presumptive preneoplastic foci and nodules from hepatocytes in chemical carcinogenesis in rat liver.

The sites and times of appearance of preneoplastic foci in rat liver acinus during the first 11 days after initiation with diethylnitrosamine and promotion with 2-acetylaminofluorene plus partial hepatectomy was observed in three separate experiments. Foci appeared as alterations of hepatocytes followed by focal proliferation in each of the three zones before any ductular epithelial cell ('oval cell') proliferation. The dissociation between foci and 'oval cell proliferation' is strong evidence against a role of the latter in generating preneoplastic hepatocytes in hepatocellular carcinogenesis.