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Oxidatively Generated Damage to DNA and Biomarkers

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Abstract

The first part of this chapter is devoted to the description of degradation pathways for DNA bases and sugar moieties in the cell that are mediated by hydroxyl radical, one-electron oxidants and singlet oxygen. Thus, 11 single modified nucleosides and nucleobases that may be part of more complex radiation-induced DNA damage have been shown to be generated in nuclear DNA. In addition, four clustered DNA addition products and one tandem base-sugar lesion that arises from •OH-mediated hydrogen abstraction at C4 and C5 of the 2-deoxyribose moiety of DNA have also been identified in cells. Mechanisms of formation that are inferred from model studies are available for the 16 single and complex lesions thus detected in nuclear DNA. The DNA oxidation products whose radiation-induced formation in cellular was found to vary between 2 and 100 per 109 normal nucleosides per Gray may be used as biomarkers of oxidative stress. The accurate measurement of single, clustered or tandem lesions was performed, once DNA was extracted and subsequently enzymatically or chemically hydrolyzed, using accurate chromatographic methods. These involve, in most cases, the association of high performance liquid chromatography with the electrospray ionization tandem mass spectrometry (HPLC-ESI/MS–MS) detection techniques operating in the highly accurate and sensitive multiple reaction monitoring mode. Another approach that is more sensitive and less prone to artefactual oxidation consists of pre-incubating oxidized DNA with repair enzymes to reveal classes of modifications as strand breaks prior to either single-cell electrophoresis analysis or alkaline elution analysis.

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  1. Laboratoire “Lésions des Acides Nucléiques”, SCIB-UMR-E n°3 (CEA/UJF), Institut Nanosciences et Cryogénie, CEA/Grenoble, Grenoble Cedex 9, 38054, France

    Jean Cadet

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  1. Jean Cadet
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  2. Thierry Douki
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  3. Jean-Luc Ravanat
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Correspondence to Jean Cadet .

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  1. Dept. Health & Caring Sciences, University Uppsala, Döbelnsgatan 2, Uppsala, 752 37, Sweden

    Samar Basu

  2. Dept. Surgical Sciences, Anaesthesiology, & Intensive Care, Uppsala University Hospital, Akademiska Sjukhuset, Uppsala, 751 85, Sweden

    Lars Wiklund

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Cadet, J., Douki, T., Ravanat, JL. (2011). Oxidatively Generated Damage to DNA and Biomarkers. In: Basu, S., Wiklund, L. (eds) Studies on Experimental Models. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-956-7_29

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