A precursor-product relationship exists between oval cells and hepatocytes in rat liver

Oval cell proliferation was induced in twelve male Fischer rats by administration of 2-acetylaminofluorene (2-AAF) for 2 weeks and by performing partial hepatectomy one week after the beginning of 2-AAF administration. Albumin expression in liver was studied by using in situ hybridization of 3H-labeled rat albumin riboprobe. Radiolabeled thymidine was administered to a group of animals at day 6 after partial hepatectomy. The animals were killed at 0, 3, 7, 9, 11 and 13 days after partial hepatectomy. Both oval cells and basophilic hepatocytes showed a prominent expression of albumin, whereas albumin expression in acidophilic pre-existing hepatocytes was decreased. Oval cell nuclei were exclusively labeled one day after administration of [3H]thymidine. At day 9, 11 and 13 basophilic hepatocytes became labeled and the area occupied by these cells increased. This is the first demonstration of the transfer of radiolabeled thymidine from oval cells to newly formed hepatocytes in vivo. Thus the precursor-product relationship between oval cells and basophilic hepatocytes has been established.