Wei H, Cai Q, Rahn R, Zhang X
Department of Dermatology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Free Radic Biol Med. 1997;23(1):148-54. doi: 10.1016/s0891-5849(96)00526-6.
In the present article, we report that ultraviolet (UV 254 nm) radiation substantially induced the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in purified DNA. The formation of 8-OHdG, a hallmarker of oxidative DNA damage, increased linearly up to 25 kJ/m2 and was dependent on the presence of oxygen in the solution. Deoxygenation by nitrogen significantly reduced the yield of 8-OHdG by UV radiation, whereas oxygenation with 100% oxygen substantially enhanced the yield. The hydroxyl radical (HO.) scavenger dimethysulfoxide (DMSO) dramatically quenched the formation of 8-OHdG by the ionizing radiation and Fenton reaction, but enhanced the formation of UV-induced 8-OHdG. Further studies showed that DMSO and mannitol, two predominant HO. scavengers, enhanced the levels of UV-induced 8-OHdG in a dose-dependent fashion, suggesting that UV-induced 8-OHdG is independent of the generation of HO.. The use of deuterium oxide (D2O), which prolongs the half life of singlet oxygen (1O2), substantially enhanced the yield of 8-OHdG by UV radiation, but not that by Fenton reaction. In contrast, sodium azide, a more and less specific 1O2 quencher, substantially reduced the levels of 8-OHdG by both UV radiation and Fenton reaction, indicating that sodium azide lacks the quenching specificity of 1O2 and HO.. It is proposed that UV induced 8-OHdG proceeds through a singlet oxygen involvement mechanism, rather than the generation of hydroxyl radicals.
在本文中，我们报告紫外线（UV 254 nm）辐射可在纯化的DNA中显著诱导8-羟基-2'-脱氧鸟苷（8-OHdG）的形成。8-OHdG是氧化性DNA损伤的一个标志，其形成量在达到25 kJ/m²之前呈线性增加，且依赖于溶液中氧气的存在。用氮气脱氧可显著降低紫外线辐射诱导的8-OHdG产量，而用100%氧气进行氧合则可大幅提高产量。羟基自由基（HO·）清除剂二甲基亚砜（DMSO）可显著抑制电离辐射和芬顿反应诱导的8-OHdG形成，但却增强了紫外线诱导的8-OHdG形成。进一步研究表明，两种主要的HO·清除剂DMSO和甘露醇以剂量依赖的方式提高了紫外线诱导的8-OHdG水平，这表明紫外线诱导的8-OHdG的形成与HO·的产生无关。使用重水（D₂O）可延长单线态氧（¹O₂）的半衰期，它可大幅提高紫外线辐射诱导的8-OHdG产量，但对芬顿反应诱导的8-OHdG产量没有影响。相比之下，叠氮化钠作为一种不太特异的¹O₂猝灭剂，可显著降低紫外线辐射和芬顿反应诱导的8-OHdG水平，这表明叠氮化钠缺乏对¹O₂和HO·的猝灭特异性。我们提出，紫外线诱导8-OHdG的形成是通过单线态氧参与机制，而非羟基自由基的产生。
