Unscheduled DNA Synthesis and Elimination of DNA Damage in Liver Cells of γ-irradiated Senescent Mice

Summary

The level of ‘spontaneous’ and γ-radiation-induced DNA synthesis which is not inhibited with hydroxyurea (unscheduled synthesis) is considerably lower in hepatocytes of 18–22-month-old mice than that of 1·5–2-month-old mice. The dose-dependent increase (10–300 Gy) of unscheduled DNA synthesis (UDS) in hepatocytes of senescent mice is higher than in young animals. The elimination of damage in DNA of γ-irradiated hepatocytes (100 Gy) was examined by using an enzyme system (M. luteus extract and DNA-polymerase I of E. coli). It was found that the rate of elimination of the DNA damage in hepatocytes of 20-month-old mice is lower than that of 2-month-old mice although the activities of DNA-polymerase β and apurinic endonuclease remain equal in the liver of both senescent and young mice. However, the nucleoids from γ-irradiated liver nuclei of 2-month-old mice are relaxed to a greater extent (as judged by the criterion of ethidium-binding capacity) than those of 20-month-old mice.

The results suggest that there are limitations in the functioning of repair enzymes and in their access to damaged DNA sites in the chromatin of senescent mouse liver cells.