HUMAN HEPATOCYTE POLYPLOIDIZATION KINETICS IN THE COURSE OF LIFE-CYCLE

The processes of polyploidization in normal human liver parenchyma fro m 155 individuals aged between 1 day and 92 years were investigated by Feulgen-DNA cytophotometry. It was shown that polyploid hepatocytes a ppear in individuals from 1 to 5 years old. Up to the age of 50 years the accumulation rate of binucleate and polyploid cells is very slow, but subsequently hepatocyte polyploidization is intensified, and in pa tients aged 86-92 years the relative number of cells with polyploid nu clei is about 27%. Only a few hepatocytes in the normal human liver re ach 16C and 8C x 2 ploidy levels for mononucleate and binucleate cells respectively. Using a mathematical modeling method, it was shown that during postnatal liver growth the polyploidization process in human l iver is similar to that in the rat, and that polyploid cells are forme d mainly from binucleate cells. As in rats, prior to an increase in pl oidy level, diploid human hepatocytes can pass several times through t he usual mitotic cycles maintaining their initial ploidy level. After birth, only one in ten hepatocytes starting DNA synthesis enters the p olyploidization process. At maturity about 60% of 2C-hepatocytes start ing DNA synthesis divide by conventional mitosis, the rest dividing by acytokinetic mitosis leading to the formation of binucleate cells. Du ring ageing the probability of hepatocyte polyploidization increases a nd in this period there are two polyploid or binucleate cells for ever y diploid dividing by conventional mitosis.