Ishikawa T, Sakurai J
Cancer Res. 1986 Mar;46(3):1344-8.
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.
由于相对于其他细胞过程的DNA修复能力是一个与诱变、致癌作用以及衰老相关的重要参数，因此对其评估最好在完整动物中进行。出于这个原因，我们开发了一种用于直接在体内测量DNA修复的放射自显影技术。通过这种方法，在用化学致癌物或紫外线（UV）照射后，非预定DNA合成（UDS）可以作为小鼠皮肤上皮细胞上的银颗粒被定量检测到。使用2个月和18个月大的小鼠，通过这种皮肤技术检查了UDS反应中可能与年龄相关的变化。在用4-羟基氨基喹啉1-氧化物处理后，在两个年龄段的小鼠中都观察到了类似的剂量依赖性UDS诱导。紫外线照射后年轻和老年动物的剂量反应曲线在低剂量时也显示出类似的增加至平台水平，但它们对高剂量的反应非常不同。在老年小鼠中，UDS水平随着剂量增加而显著下降，而在年轻小鼠中它保持在相同的平台水平。这表明，在老年动物中，高剂量的紫外线照射会导致DNA修复系统恶化，并且老年动物不能有效地修复广泛的紫外线诱导的DNA损伤。
