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-Far ber model). Liver cells were pulse-chase labelled with bromodeoxyuridi ne (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) similar to 10 times higher than that of the hepatocytes as analyse d by flow cytometry (FCM)), the majority of the proliferating cells be ing oval cells. At later time points, there was no significant increas e in the LI of diploid hepatocytes, and no detectable shift of BrdU-la belled cells from the NPC fraction to the hepatocyte fraction, suggest ing that no extensive conversion of BrdU-labelled oval cells to hepato cytes 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-labelle d 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 hepato cytes may thus explain the large increase in the diploid hepatocyte fr action 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.