Oxidatively Generated Damage to DNA and Biomarkers

作者: Jean Cadet , Thierry Douki , Jean-Luc Ravanat

DOI: 10.1007/978-1-60761-956-7_29

关键词: BiochemistryElectrospray ionizationDNA oxidationNuclear DNATandem mass spectrometryChemistryNucleobaseSelected reaction monitoringDNADNA damage

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

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