PROLIFERATION OF DIPLOID HEPATOCYTES AND NONPARENCHYMAL (OVAL) CELLS DURING RAT-LIVER REGENERATION IN THE PRESENCE OF 2-ACETYLAMINOFLUORENE

Treatment of rats with the carcinogen 2-acetylaminofluorene (2-AAF) du ring liver regeneration (Solt-Farber protocol) induced a selective out growth of diploid, gamma-glutamyltranspeptidase (GGT)-positive hepatoc ytes (3-4 times increase) as well as of nonparenchymal (oval) liver ce lls. After cessation of treatment the oval cells rapidly disappeared, while the population of diploid, GGT-positive hepatocytes declined mor e slowly over the subsequent ten weeks. In animals pretreated with the initiating carcinogen diethylnitrosamine (DEN) a large fraction of th e diploid, GGT-positive hepatocytes persisted. The results differ from those obtained with our standard, sequential treatment protocol (2-AA F given after completed regeneration), where there is no hyperprolifer ation of oval cells and where GGT-positive hepatocytes are found only in DEN-pretreated animals (Saeter et al, Carcinogenesis 9: 581-587, 19 88). Different experimental models of liver carcinogenesis may thus pr esent different patterns of liver cell proliferation, which should be taken into account when general hypotheses on the cellular origin of l iver cancer are proposed.