Immediate-early gene expression during regenerative and mitogen-induced liver growth in the rat

The nongenotoxic carcinogens phenobarbitone (PB) and methyl clofenapate (MCP) and the hepatomitogen pregnenolone 16 alpha carbonitrile (PCN) are direct inducers of hepatic S-phase in rats, whereas the S-phase seen after partial hepatectomy is regenerative. We have investigated S-phase and immediate-early gene expression (c-myc and c-jun) in rat liver following these treatments to study the differences in gene expression associated with direct vs. regenerative responses. Both partial hepatectomy (one- and two-thirds) and mitogen treatment caused an increase in hepatic S-phase that peaked around 36 hours. Two-thirds partial hepatectomy caused the greatest increase in S-phase followed by one-third partial hepatectomy, then the mitogens PCN, MCP, and PB in that order. This order of response was also seen with c-jun and to a lesser degree with c-myc expression, suggesting that immediate-early gene expression might be linked not only to regenerative S-phase but also to direct mitogen-induced responses.