Singlet oxygen involvement in ultraviolet (254 nm) radiation-induced formation of 8-hydroxy-deoxyguanosine in DNA

Singlet oxygen involvement in ultraviolet (254 nm) radiation-induced formation of 8-hydroxy-deoxyguanosine in DNA
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DOI:
10.1016/s0891-5849(96)00526-6
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发表时间:
1997-01-01
影响因子:
7.4
通讯作者:
Zhang, XS
Zhang, XS
中科院分区:
医学1区
文献类型:
--
作者:
Wei, HC;Cai, QY;Zhang, XS

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在本文中,我们报道了紫外线(UV 254 nm)辐射在纯化的DNA中大量诱导8-羟基-2'-脱氧鸟苷(8-OHdG)的形成。8-OHdG的形成,DNA氧化损伤的标志,线性增加到25 kJ/m(2),并依赖于溶液中氧气的存在。氮脱氧显著降低了紫外辐射8-OHdC的产率,而100%氧氧化则显著提高了产率。羟基自由基(HO .)清除剂二甲基亚砜(DMSO)通过电离辐射和Fenton反应显著抑制8-OHdG的形成,但增强了紫外线诱导的8-OHdG的形成。进一步的研究表明,DMSO和甘露醇是两种主要的HO。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与HO的产生无关。氧化氘(D2O)的使用延长了单线态氧(O-1(2))的半衰期,显著提高了紫外辐射下8-OHdG的产率,但芬顿反应的产率没有提高。而叠氮化钠作为一种对O-1(2)的猝灭剂,在UV辐射和Fenton反应下均能显著降低8-OHdC的水平,说明叠氮化钠对O-1(2)和HO缺乏猝灭特异性。提出紫外线诱导的8-OHdG是通过单线态氧参与机制进行的,而不是产生羟基自由基。(C) 1997爱思唯尔科学有限公司
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/m(2) and was dependent on the presence of oxygen in the solution. Deoxygenation by nitrogen significantly reduced the yield of 8-OHdC 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 (O-1(2)), 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 O-1(2) quencher, substantially reduced the levels of 8-OHdC by both UV radiation and Fenton reaction, indicating that sodium azide lacks the quenching specificity for O-1(2) and HO .. It is proposed that UV induced 8-OHdG proceeds through a singlet oxygen involvement mechanism, rather than the generation of hydroxyl radicals. (C) 1997 Elsevier Science Inc.