Cadet Jean, Davies Kelvin J A, Medeiros Marisa Hg, Di Mascio Paolo, Wagner J Richard
Département de médecine nucléaire et radiobiologie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4.
Leonard Davis School of Gerontology of the Ethel Percy Andrus Gerontology Center, The University of Southern California, Los Angeles, CA 90089-0191, United States; Division of Molecular & Computational Biology, Department of Biological Sciences of the Dornsife College of Letters, Arts, and Sciences, The University of Southern California, Los Angeles, CA 90089-0191, United States.
Free Radic Biol Med. 2017 Jun;107:13-34. doi: 10.1016/j.freeradbiomed.2016.12.049. Epub 2017 Jan 2.
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 10 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.
在这篇综述文章中，重点在于对有关修饰核苷酸碱基和2-脱氧核糖产物的现有数据进行批判性审视，这些产物是在细胞DNA暴露于多种氧化物种和试剂后被鉴定出来的，这些氧化物种和试剂包括羟基自由基、单电子氧化剂、单线态氧、次氯酸和十一-易位酶。此外，还提供了有关8-氧代-7,8-二氢鸟嘌呤的二次氧化产物以及脂质过氧化物分解产生的具有反应性醛的核苷酸碱基加成产物生成情况的信息。值得注意的是，基于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，明确鉴定并定量检测了由单损伤、链内和链间交联组成的不同类型的氧化诱导DNA损伤。报道的数据清楚地表明，在包括暴露于电离辐射在内的严重氧化条件下产生的DNA损伤频率很低，每10个正常碱基中最多只有几个修饰。准确分析测量方法的应用还使得能够确定细胞DNA中几种明确损伤的修复动力学，然而到目前为止，这仅涉及有限数量的案例。
