KINETICS OF HEPATOCYTE GROWTH FACTOR-INDUCED DNA-SYNTHESIS INVITRO - A COMPARATIVE-STUDY WITH EPIDERMAL GROWTH-FACTOR AND INSULIN

Objective: To describe the kinetics of in vitro hepatocyte proliferation induced by a range of doses of hepatocyte growth factor (HGF) compared with those seen with epidermal growth factor (EGF). Hepatocyte growth factor with/without insulin, or EGF with insulin, were added to primary rat hepatocytes 20 h after plating. Methods: The cumulative fraction of cells with nuclear labelling following the addition of H-3-thymidine was determined by autoradiography at intervals from 32-66 h. Results: Several cell cycle parameters were determined. Hepatocyte growth factor and EGF were shown to have identical pre-replicative lag times (17 h) at all doses. Entry of hepatocytes into DNA synthesis after stimulation with HGF obeyed first order kinetics, as does entry after ECF stimulation. The maximal rate constant for the rate of entry into DNA synthesis (kG1/S) was significantly greater for HCF (0.0229/h) and HGF with insulin (0.0275/h) than EGF with insulin (0.0194/h; P<0.005). Conclusion: Hepatocyte growth factor acts as a strong proliferative stimulus at the G1 to S interface, compatible with the hypothesis that it is a major physiological stimulus to liver regeneration.