Oxidatively generated base damage to cellular DNA

Search for the formation of oxidatively base damage in cellular DNA has been a matter of debate for more than 40 years due to the lack of accurate methods for the measurement of the lesions. HPLC associated with either tandem mass spectrometry (MS/MS) or electrochemical detector (ECD) together with...

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Bibliographic Details
Published in:Free radical biology & medicine 2010-07, Vol.49 (1), p.9-21
Main Authors: Cadet, Jean, Douki, Thierry, Ravanat, Jean-Luc
Format: Article
Language:English
Subjects:
Analytical chemistry
Animals
Chemical Sciences
Chromatography, High Pressure Liquid
DNA biomarkers
DNA Damage
HPLC-MS/MS measurements
Humans
Hydroxyl radical
Life Sciences
Lipid Peroxidation
Lipid peroxides
Nucleosides - chemistry
Nucleosides - genetics
One-electron oxidants
Oxidants - adverse effects
Oxidation reactions
Oxidative Stress
Oxidized DNA bases
Oxygen singulet
Radiation, Ionizing
Reactive aldehydes
Tandem Mass Spectrometry
Toxicology
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Summary:Search for the formation of oxidatively base damage in cellular DNA has been a matter of debate for more than 40 years due to the lack of accurate methods for the measurement of the lesions. HPLC associated with either tandem mass spectrometry (MS/MS) or electrochemical detector (ECD) together with optimized DNA extraction conditions constitutes a relevant analytical approach. This has allowed the accurate measurement of oxidatively generated single and clustered base damage in cellular DNA following exposure to acute oxidative stress conditions mediated by ionizing radiation, UVA light and one-electron oxidants. In this review the formation of 11 single base lesions that is accounted for by reactions of singlet oxygen, hydroxyl radical or high intensity UVC laser pulses with nucleobases is discussed on the basis of the mechanisms available from model studies. In addition several clustered lesions were found to be generated in cellular DNA as the result of one initial radical hit on either a vicinal base or the 2-deoxyribose. Information on nucleobase modifications that are formed upon addition of reactive aldehydes arising from the breakdown of lipid hydroperoxides is also provided.
ISSN:0891-5849
1873-4596
DOI:10.1016/j.freeradbiomed.2010.03.025