Oxidatively generated base damage to cellular DNA

被引：420

作者：

Cadet, Jean ^{[1
,2
]}

Douki, Thierry ^{[1
]}

Ravanat, Jean-Luc ^{[1
]}

机构：

[1] CEA UJF, INAC, Lab Les Acides Nucle, CEA Grenoble,SCIB UMR E 3, F-38054 Grenoble 9, France

[2] Univ Sherbrooke, Dept Med Nucl & Radiobiol, Fac Med Sci Sante, Sherbrooke, PQ J1H 5N4, Canada

来源：

FREE RADICAL BIOLOGY AND MEDICINE | 2010年 / 49卷 / 01期

关键词：

Oxidized DNA bases; Oxidation reactions; DNA biomarkers; Hydroxyl radical; Oxygen singulet; One-electron oxidants; Lipid peroxides; Reactive aldehydes; HPLC-MS/MS measurements; PERFORMANCE LIQUID-CHROMATOGRAPHY; ONE-ELECTRON OXIDATION; CROSS-LINK LESION; TEMPERATURE PHOTOSENSITIZED OXIDATION; RADIATION-MEDIATED DAMAGE; UV LASER PHOTOLYSIS; GAMMA-RADIATION; SINGLET OXYGEN; LIPID-PEROXIDATION; GUANINE OXIDATION;

D O I：

10.1016/j.freeradbiomed.2010.03.025

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Search for the formation of oxidatively base damage in cellular DNA has been a matter of debate for more than 40 years due to the lack of accurate methods for the measurement of the lesions. HPLC associated with either tandem mass spectrometry (MS/MS) or electrochemical detector (ECD) together with optimized DNA extraction conditions constitutes a relevant analytical approach. This has allowed the accurate measurement of oxidatively generated single and clustered base damage in cellular DNA following exposure to acute oxidative stress conditions mediated by ionizing radiation. UVA light and one-electron oxidants. In this review the formation of 11 single base lesions that is accounted for by reactions of singlet oxygen, hydroxyl radical or high intensity UVC laser pulses with nucleobases is discussed on the basis of the mechanisms available from model studies. In addition several clustered lesions were found to be generated in cellular DNA as the result of one initial radical hit on either a vicinal base or the 2-deoxyribose. Information on nucleobase modifications that are formed upon addition of reactive aldehydes arising from the breakdown of lipid hydroperoxides is also provided. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：9 / 21

页数：13

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