Polyploidy associated with oxidative injury attenuates proliferative potential of cells

Polyploid cells are encountered ubiquitously but the biological significanc e of polyploidy is unclear. In view of their extensive capacity for regener ation, hepatocytes offer excellent systems for analyzing growth control mec hanisms. We isolated hepatocytes from adult rats with and without two-third partial hepatectomy, which induces hepatic polyploidy. Polyploid hepatocyt es showed evidence for oxidative injury with antioxidant depletion, lipid p eroxidation and 8-hydroxy-adducts of guanine in nuclear DNA. Liver repopula tion assays in intact animals showed markedly decreased replication capacit y in polyploid hepatocytes. Recapitulation of polyploidy in cultured hepato cytes established that mitogenic stimulation in the presence of oxidative D NA injury was capable of inducing polyploidy. The findings provide novel fr ameworks in the context of polyploidy for understanding tissue development, regeneration and oncogenesis.