VARIATIONS OF HEPATIC ANTIOXIDANT SYSTEMS AND DNA-PLOIDY IN RATS AGED2 TO 8 MONTHS

Oxygen-reactive species are by-products of biological redox reactions and are involved in the development and aging processes. In order to t est whether the time-dependent changes in the hepatic antioxidant defe nse are related to changes in DNA ploidy, we studied in rats, aged 2-8 months, the enzymes and metabolites related to the primary cell defen se against oxidative stress, as well as the distribution of DNA into t he cell cycle phases. Catalase and glutathione peroxidase, together wi th glutathione reductase and mitochondrial superoxide dismutase, under went progressive and significant time course increases. Although no te mporal changes were observed in the concentration of protein thiol gro ups and malondialdehyde in rats in the same age period, glutathione re dox state, detected by the GSH/GSSG ratio decreased significantly to 4 1% (P < 0.001) of the initial value. DNA content was assayed by flow c ytometry in isolated hepatocytes, and changes in DNA ploidy and distri bution in the cell cycle phases were determined. A sharp decrease in d iploid population from rats aged 1-8 months (92.9% --> 11.1%) and a pr onounced increase in hepatocyte polyploid populations in the same age period (2.6% --> 87.3%) were observed. However, liver cell population involved in S phase (DNA synthesis) was unchanged. These results indic ate that the cell defense mechanisms against oxygen toxicity increased in liver of rats from 2-8 months in order to suppress the oxidative i mbalance. During the 6-month period of a rat's life (2-8 months), the significant alterations of GSH/GSSG ratio to a more oxidative state ha ve no influence on the proliferating capacity of the cells.