Cellular and Molecular Changes in Early Stages of Hepatocarcinogenesis
The role of oval cells in liver regeneration and carcinogenesis remains controversial1–7. After partial hepatectomy no significant proliferation of oval cells is observed even though the liver undergoes a rapid restoration of its mass. In contrast, a prominent oval cell proliferation is frequently observed after the administration of carcinogens, especially azo-dyes and 2-AAF1–6. Oval cell proliferation is also observed when mature hepatocytes are unable to proliferate, due to nutritional and toxic effects of chemicals7. The fate of these oval cells particularly as it relates to questions regarding the precursor-product relationship to normal hepatocytes and histogenesis of hepatocellular carcinoma is a matter of considerable controversy (for review, see ref. 8). In the Solt-Farber protocol for production of hepatocellular carcinomas, administration of 2-AAF is used for selective growth inhibition of non-initiated hepatocytes, whereas partial hepatectomy provides a potent growth stimulus for resistant “initiated” hepatocytes9. In our earlier studies using in situ hybridization technique we observed a peculiar distribution of albumin mRNA in the liver two weeks after partial hepatectomy in Solt-Farber rats10. The albumin mRNA was present almost exclusively in rounded basophilic areas, some of which were gamma-glutamyl transpeptidase (GGT) positive, but many of them were negative for GGT10. Thus a severe “inhibition” of albumin expression was observed in the majority of the “old” hepatocytes, whereas the “new” basophilic hepatocytes were efficiently expressing the albumin gene. We therefore wanted to reexamine the effect of 2-AAF administration combined with partial hepatectomy, but without any initiating agent, on the expression of albumin mRNA using in situ hybridization. In addition, the role of oval cells as possible precursors of the basophilic albumin positive hepatocytes was addressed by studying the transfer of radiolabeled thymidine from oval cells to basophilic hepatocytes11.
KeywordsOval Cell Partial Hepatectomy Basophilic Cell Thymidine Label Mature Hepatocyte
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