The goals of our work are to determine the extent to which mRNA populations of adult, immature, regenerating, and neoplastic rat liver may differ quantitatively and qualitatively from each other and to identify messenger RNAs (mRNA) and sets of active genes that might be specific for a certain growth pattern. We have demonstrated that transcripts of the H-ras, Ki-ras and myc oncogenes increase in abundance (3 to 10 times) at the time of DNA synthesis during liver regeneration induced by partial hepatectomy or chemical injury and return to normal after the major wave of DNA synthesis has ended. This is the first demonstration of a regulated expression of oncogenes during a physiological growth process. Other oncogenes are either not expressed in the liver (mos) or do not change their expression during the regenerative growth process. We have separated, by centrifugal elutriation, different cell populations from preneoplastic rat livers. An analysis of the expression of several oncogenes in these isolated cell populations indicates that the myc and ki-ras transcripts are more abundant in oval cells and that their expression is elevated during all stages of carcinogenesis and in primary tumors. In contrast, H-ras expression is transiently elevated in hepatocytes at the earliest stages of carcinogenesis. Further characterization of these cell populations, done by analyzing the expression of multiple transcripts from the AFP gene, indicates that oval cells may constitute a compartment of faculative stem cells in the normal liver that might be capable of generating normal and abnormal hepatocytes under appropriate stimuli. (G)
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