Ontogeny of hepatocyte proliferation inhibitor activity during human liver development and its effect on cell proliferation in in vivo and in vitro studies

Abstract

Ontogeny of hepatocyte proliferation inhibitory (HPI) activity was studied during human liver development. HPI activity was first noticed in the cytosolic fraction of 20-week-old fetal liver and thereafter it began to increase with the liver maturation. An inverse correlation between the ontogeny of HPI activity and mitotic counting of the hepatocytes during human liver development was established. The crude HPI fraction from fetal and adult human liver inhibited the incorporation of [3H]thymidine into the DNA of 2-day-old rat liver and HepG2 cells and the inhibitory effect was directly proportional to the age of the HPI source. Prolonged exposure of HepG2 cells to the HPI fraction was also found to be cytotoxic. Preliminary characterization of the crude HPI fraction revealed an age-dependent increase in proteins of 18, 28, and 60 kilodaltons following silver chloride staining of sodium dodecyl sulfate - polyacrylamide gel electrophoresis and densitometric scanning.Key words: human liver, hepatocyte proliferation inhibitor, ontogeny, sodium dodecyl sulfate - polyacrylamide gel electrophoresis, HepG2 cells, cytotoxic.