Formation and repair of oxidatively generated damage in cellular DNA

• Published in: Free radical biology & medicine Vol. 107; pp. 13 - 34
• Main Authors: Cadet, Jean, Davies, Kelvin J.A., Medeiros, Marisa HG, Di Mascio, Paolo, Wagner, J. Richard
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2017
• Subjects: Animals; Chromatography, High Pressure Liquid; Dioxygenases - metabolism; DNA Adducts; DNA Damage; DNA oxidative degradation pathways; DNA Repair; Humans; Lipid Peroxidation; Measurement of oxidatively generated DNA damage; Oxidative Stress; Radiation, Ionizing; Reactive Oxygen Species - metabolism; Repair of oxidized bases; Single base oxidation modifications; Spectrometry, Mass, Electrospray Ionization; DNA oxidative degradation pathways; Repair of oxidized bases; Single base oxidation modifications; Measurement of oxidatively generated DNA damage
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2016.12.049

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. [Display omitted] •HPLC based methods are appropriate for monitoring oxidatively damage to DNA.•Single base lesions, intra- and interstrand cross-links were identified in cellular DNA.•Other modifications included halogenated bases and adducts with reactive aldehydes.•Paucity of reliable data on the base excision repair of oxidized bases in cells.