Current Molecular Medicine

David W. Li  
College of Medicine
University of Nebraska Medical Center
Omaha, NE
USA

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Oxidatively Generated DNA Lesions as Potential Biomarkers of In Vivo Oxidative Stress

Author(s): J.-L. Ravanat, J. Cadet and T. Douki

Affiliation: Laboratoire Lesions des Acides Nucleiques, INAC/SCIB (UMR-E3 CEA-UJF), CEA Grenoble, 17 rue des Martyrs, F38054 Grenoble Cedex 9, France.

Keywords: Biomarkers, DNA chemistry, DNA damage, DNA repair, oxidative stress, tandem mass spectrometry, anti-oxidants, apoptosis, 8-oxodGuo, oxidation, diamagnetic compounds, reactive nitrogen species, peroxinitrite, hypochlorite acid, ozone

Abstract:

During the last three decades there was an increasing interest for developing biomarkers of oxidative stress. Therefore, efforts have been made to develop sensitive methods aimed at measuring cellular levels of oxidatively generated DNA lesions. Initially, most attention had focused on 8-oxo-7,8-dihydro-2’- deoxyguanosine (8-oxodGuo) probably because reliable analytical methods (mostly HPLC coupled to electrochemical detection) were available since mid-eighties to detect that lesion at the cellular level. With the recent development of more versatile analytical (using mass spectrometric detection) and biochemical assays (such as the comet assay) efforts are currently made to measure simultaneously several DNA lesions. The main degradation pathways of the four main pyrimidine (thymine, cytosine) and purine (adenine, guanine) bases mediated by hydroxyl radical (•OH), one-electron oxidants and singlet oxygen (1O2) have been also studied in detail and results indicate that other DNA modification than 8-oxodGuo could represent suitable biomarkers of oxidative stress. In this review article, the main oxidative degradation products of DNA will be presented together with their mechanisms of formation. Then the developed methods aimed at measuring cellular levels of oxidatively generated DNA lesions will be critically reviewed based on their specificity, versatility and sensitivity. Illustration of the powerfulness of the described methods will be demonstrated using quantification of DNA lesions in cells exposed to ionizing radiations. In addition, recent work highlighting the possible formation of complex DNA lesions will be reported and commented regarding the possibility of using such complex damage as potential biomarkers of oxidative stress.

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Article Details

VOLUME: 12
ISSUE: 6
Page: [655 - 671]
Pages: 17
DOI: 10.2174/156652412800792651