In vivo studies on age dependency of DNA repair with age in mouse skin

Since the capacity for DNA repair relative to other cellular processes is an important parameter relevant to mutagenesis, carcinogenesis, and also aging, its assessment should preferably be carried out in intact animals. For this reason we developed an autoradiographic technique for measuring DNA repair directly in vivo. By this method unscheduled DNA synthesis (UDS) can be detected quantitatively as silver grains over epithelial cells of mouse skin after treatment with chemical carcinogens or ultraviolet (UV) irradiation. Possible age-related change in UDS response was examined by this skin technique using 2- and 18-mo-old mice. Similar dose-dependent induction of UDS was observed in mice of both ages after treatment with 4-hydroxyaminoquinoline 1-oxide. The dose-response curves for young and aged animals after UV irradiation also showed similar increases to a plateau level at low doses, but their responses to high doses were very different. In aged mice the UDS level decreased markedly with increase in dose, whereas in young mice it remained at the same plateau level. This suggests that, in aged animals, high doses of UV irradiation cause deterioration of DNA repair systems, and that aged animals cannot repair extensive UV-induced DNA damage efficiently.