DEFEROXAMINE ARRESTS IN-VITRO THE PROLIFERATION OF PORCINE HEPATOCYTEIN G1 PHASE OF THE CELL-CYCLE

Iron is required for cell proliferation of all living species. Moreove r, iron excess may be involved in the development of hepatocellular ca rcinoma. In this study we analyzed the effects of deferoxamine, an iro n chelator, on normal porcine hepatocyte proliferation. We confirmed t hat hepatocytes isolated from young pigs proliferate in the presence o f insulin and fetal calf serum as shown by [H-3] methyl-thymidine inco rporation, presence of mitotic figures and increase in cell number. Th is was paralleled by nuclear expression of p34(cdc2) and its associate d histone H1 kinase activity. In the presence of deferoxamine, [H-3] m ethyl-thymidine incorporation, expression of nuclear proteins (p34(cdc 2) and PCNA) and H1 kinase activity were drastically reduced. In addit ion, in contrast with control cultures, cells in S-phase were not dete cted by flow cytometry. These data suggest that iron chelation by defe roxamine can arrest the progression of porcine hepatocytes in the G1 p hase of the cell cycle.