The trap depth (in DNA) of 8-oxo-7,8-dihydro-2′deoxyguanosine as derived from electron-transfer equilibria in aqueous solution
The trap depth (in DNA) of 8-oxo-7,8-dihydro-2′deoxyguanosine as derived from electron-transfer equilibria in aqueous solution
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DOI：
10.1021/ja993508e
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发表时间：
2000-03-15
影响因子：
15
通讯作者：
Bernhard, K
中科院分区：
文献类型：
--
作者：
Steenken, S;Jovanovic, SV;Bernhard, K
8-氧代-7，8-二氢-2‘脱氧鸟苷(≡8-O-HDG)，通常被称为8-羟基-2’脱氧鸟苷(8-O-HDG)，可能是生物系统中最重要和最有文献记载的氧化应激产物。事实上，它在细胞DNA中的浓度是对有机体遭受的损害程度的定量衡量。8-12除非8-OHdG是自然界中故意植入DNA的，否则它是2‘-脱氧鸟苷(DG)氧化分解的产物。已经确定了从DG到其8-羟基衍生物的大量氧化剂/氧化环境，其中一些更重要的是单线态氧，13，14 OH自由基(由电离辐射或过渡金属催化的过氧化氢分解产生)，15，16和光氧化17(据信18-21通过鸟苷自由基阳离子进行)。8-OHdG是一种与癌症和衰老有关的突变损伤，8，22，但这样它不会导致DNA链断裂。然而，它比它的天然“母体”DG，14，21，23-26更容易氧化，其氧化产物是(哌啶诱导的)链断裂的候选者。鉴于这种明显的敏感性，有必要充分了解自由基化学
8-Oxo-7, 8-dihydro-2′ deoxyguanosine (pKa1) 8.6, pKa2) 11.7), 3 frequently called 8-hydroxy-2′ deoxyguanosine (≡ 8-O-HdG), is probably the most important and best-documented product of “oxidative stress” 4-7 in biological systems. Its concentration in the cellular DNA is, in fact, a quantitative measure of the degree of damage that an organism has undergone. 8-12 Unless 8-OHdG is built by nature into DNA on purpose, it is the product of oxidative decomposition of 2′ deoxyguanosine (dG). A large number of oxidants/oxidizing environments leading from dG to its 8-hydroxy derivative have been identified, some of the more important ones being singlet oxygen, 13, 14 the OH radical (produced by ionizing radiation or transition metal catalyzed decomposition of hydroperoxides), 15, 16 and photo-oxidation17 (which is believed18-21 to proceed via the guanosine radical cation).8-OHdG is a mutagenic lesion involved in carcinogenesis and aging, 8, 22 but as such it does not lead to DNA strand breakage. However, it is much more easily oxidized than its natural “parent”, dG, 14, 21, 23-26 and its oxidation product is a candidate for (piperidine-induced) strand breakage. 27-29 In view of this pronounced sensitivity, it is necessary to fully understand the radical chemistry