Title:Oxidatively Generated DNA Lesions as Potential Biomarkers of In Vivo Oxidative Stress
Volume: 12
Issue: 6
Author(s): J.-L. Ravanat, J. Cadet and T. Douki
Affiliation:
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.