Flow cytometric investigation of a possible precursor--product relationship between oval cells and parenchymal cells in the rat liver.

The question of a possible precursor--product relationship between oval cells and hepatocytes was examined in rats treated for 2 weeks with 2-acetylaminofluorene (2-AAF) with a two-thirds partial hepatectomy (PH) performed after the first week of 2-AAF treatment (modified Solt-Farber model). Liver cells were pulse-chase labelled with bromodeoxyuridine (BrdU) on day 6 post PH. On day 7 post PH the nonparenchymal (NPC) fraction, which contains the oval cells, exhibited a labelling index (LI) approximately 10 times higher than that of the hepatocytes as analysed by flow cytometry (FCM), the majority of the proliferating cells being oval cells. At later time points, there was no significant increase in the LI of diploid hepatocytes, and no detectable shift of BrdU-labelled cells from the NPC fraction to the hepatocyte fraction, suggesting that no extensive conversion of BrdU-labelled oval cells to hepatocytes was taking place. Throughout the experimental period there was a significant increase in the diploid hepatocyte cell fraction, from 12% on day 7 to 25% on day 13 post PH. Diploid hepatocytes pulse-labelled on days 7 or 9 post PH had a high LI (7-8%), in contrast to the low LI (1%) of tetra- and octoploid cells. Proliferation of diploid hepatocytes may thus explain the large increase in the diploid hepatocyte fraction observed from days 9 through 15 post PH. Our results, therefore, provide no reason to invoke oval cells as precursors of hepatocytes in the modified Solt-Farber carcinogenesis model.