Oxidative-stress-induced damage to DNA includes a multitude of lesions, many of which are mutagenic and have multiple roles in cancer and aging. Many lesions have been characterized by MS-based methods after extraction and digestion of DNA. These preparation steps may cause spurious base oxidation, which is less likely to occur with methods such as the comet assay, which are based on nicking of the DNA strand at modified bases, but offer less specificity. The European Standards Committee on Oxidative DNA Damage has concluded that the true levels of the most widely studied lesion, 8-oxodG (8-oxo-7,8-dihydro-2′-deoxyguanosine), in cellular DNA is between 0.5 and 5 lesions per 106 dG bases. Base excision repair of oxidative damage to DNA can be assessed by nicking assays based on oligonucleotides with lesions or the comet assay, by mRNA expression levels or, in the case of, e.g., OGG1 (8-oxoguanine DNA glycosylase 1), responsible for repair of 8-oxodG, by genotyping. Products of repair in DNA or the nucleotide pool, such as 8-oxodG, excreted into the urine can be assessed by MS-based methods and generally reflects the rate of damage. Experimental and population-based studies indicate that many environmental factors, including particulate air pollution, cause oxidative damage to DNA, whereas diets rich in fruit and vegetables or antioxidant supplements may reduce the levels and enhance repair. Urinary excretion of 8-oxodG, genotype and expression of OGG1 have been associated with risk of cancer in cohort settings, whereas altered levels of damage, repair or urinary excretion in case-control settings may be a consequence rather than the cause of the disease.
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October 2008
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Conference Article|
September 19 2008
Biomarkers of oxidative damage to DNA and repair
Steffen Loft;
Steffen Loft
1
1Department of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark
1To whom correspondence should be addressed (email [email protected]).
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Pernille Høgh Danielsen;
Pernille Høgh Danielsen
1Department of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark
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Lone Mikkelsen;
Lone Mikkelsen
1Department of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark
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Lotte Risom;
Lotte Risom
1Department of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark
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Lykke Forchhammer;
Lykke Forchhammer
1Department of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark
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Peter Møller
Peter Møller
1Department of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark
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Publisher: Portland Press Ltd
Received:
April 30 2008
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem Soc Trans (2008) 36 (5): 1071–1076.
Article history
Received:
April 30 2008
Citation
Steffen Loft, Pernille Høgh Danielsen, Lone Mikkelsen, Lotte Risom, Lykke Forchhammer, Peter Møller; Biomarkers of oxidative damage to DNA and repair. Biochem Soc Trans 1 October 2008; 36 (5): 1071–1076. doi: https://doi.org/10.1042/BST0361071
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