Formation and repair of oxidatively generated damage in cellular DNA.
Formation and repair of oxidatively generated damage in cellular DNA.
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DOI：
10.1016/j.freeradbiomed.2016.12.049
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发表时间：
2017-06
影响因子：
7.4
通讯作者：
Wagner JR
中科院分区：
文献类型：
--
作者：
Cadet J;Davies KJA;Medeiros MH;Di Mascio P;Wagner JR
在这篇综述文章中，重点是对有关修饰核碱基和 2-脱氧核糖产物的现有数据进行严格调查，这些修饰核碱基和 2-脱氧核糖产物已在暴露于各种氧化物质和试剂（包括羟自由基、单电子氧化剂、单线态氧、次氯酸和 10-11 易位酶）后在细胞 DNA 中鉴定出。此外，还提供了有关 8-oxo-7,8-二氢鸟嘌呤二次氧化产物的生成以及脂质过氧化物分解产生的反应性醛的核碱基加成产物的信息。值得注意的是，由单一损伤、链内和链间交联组成的不同类别的氧化产生的 DNA 损伤是在大多数情况下涉及高效液相色谱与电喷雾电离串联质谱联用的精确测量的基础上明确分配和定量检测的。报道的数据清楚地表明，在严重的氧化条件下（包括暴露于电离辐射）产生的 DNA 损伤的频率很低，最多每 106 个正常碱基产生一些修饰。精确分析测量方法的应用还可以确定细胞 DNA 中几个明确损伤的修复动力学，但迄今为止仅涉及有限数量的病例。
In this review article, emphasis is placed on the critical survey of available data concerning modified nucleobase and 2-deoxyribose products that have been identified in cellular DNA following exposure to a wide variety of oxidizing species and agents including, hydroxyl radical, one-electron oxidants, singlet oxygen, hypochlorous acid and ten-eleven translocation enzymes. In addition, information is provided about the generation of secondary oxidation products of 8-oxo-7,8-dihydroguanine and nucleobase addition products with reactive aldehydes arising from the decomposition of lipid peroxides. It is worth noting that the different classes of oxidatively generated DNA damage that consist of single lesions, intra- and interstrand cross-links were unambiguously assigned and quantitatively detected on the basis of accurate measurements involving in most cases high performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry. The reported data clearly show that the frequency of DNA lesions generated upon severe oxidizing conditions, including exposure to ionizing radiation is low, at best a few modifications per 106 normal bases. Application of accurate analytical measurement methods has also allowed the determination of repair kinetics of several well-defined lesions in cellular DNA that however concerns so far only a restricted number of cases.