ACTIVATION OF NUCLEAR PROTOONCOGENES AND ALPHA-FETOPROTEIN GENE IN RAT-LIVER DURING THE ACUTE INFLAMMATORY REACTION

Nuclear protooncogene and alpha-fetoprotein gene expression is stimula ted in hepatocytes during liver regeneration and by various growth fac tors in vitro. Metabolic adaptation of hepatocytes has been implicated in such gene reprogrammation. We examine here whether induction of an acute inflammation, a physiological situation of important metabolic adjustments, also triggers activation of nuclear oncogenes and of the AFP gene in rat liver. C-fos c-jun and c-mvc mRNA accumulated on North ern blots between 4-12 h of inflammation and the steady-state level of two small alpha-fetoprotein transcripts characteristic of the adult l iver increased at 4 h and 24 h of inflammation. In situ hybridization showed accumulation of the mRNA of the four genes studied in all hepat ocytes, without any zonal lobular heterogeneity. H-3-histoautoradiogra phy and mitotic counts indicated an inhibition of DNA synthesis and mi tosis, prolonged for at least 48 h after inflammation. Thus acute infl ammation triggers the activation of' nuclear protooncogenes and alpha- fetoprotein gene in hepatocytes, but this activation is not followed b y passage into the replicative cycle.