title: Urinary excretion of 8-oxo-7,8-dihydroguanine as biomarker of oxidative damage to DNA.
abstract: Oxidatively damaged DNA may be important in carcinogenesis. 8-Oxo-7,8-dihydroguanine (8-oxoGua) is an abundant and mutagenic lesion excised by oxoguanine DNA glycosylase 1 (OGG1) and measurable in urine or plasma by chromatographic methods with electrochemical or mass spectrometric detectors, reflecting the rate of damage in steady state. A common genetic OGG1 variant may affect the activity and was associated with increased levels of oxidized purines in leukocytes without apparent effect on 8-oxoGua excretion or major change in cancer risk. 8-OxoGua excretion has been associated with exposure to air pollution, toxic metals, tobacco smoke and low plasma antioxidant levels, whereas fruit and vegetable intake or dietary interventions showed no association. In rodent studies some types of feed may be source of 8-oxoGua in collected urine. Of cancer therapies, cisplatin increased 8-oxoGua excretion, whereas radiotherapy only showed such effects in experimental animals. Case-control studies found high excretion of 8-oxoGua in relation to cancer, dementia and celiac disease but not hemochromatosis, although associations could be a consequence rather than reflecting causality of disease. One prospective study found increased risk of developing lung cancer among non-smokers associated with high excretion of 8-oxoGua. Urinary excretion of 8-oxoGua is a promising biomarker of oxidatively damaged DNA.
authors.affiliation: Department of Public Health, Section of Environmental Health, University of Copenhagen, Denmark.
authors.forename: Steffen
authors.initials: S
authors.lastname: Loft
authors.forename: Pernille
authors.initials: P
authors.lastname: Danielsen
authors.forename: Mille
authors.initials: M
authors.lastname: Løhr
authors.forename: Kim
authors.initials: K
authors.lastname: Jantzen
authors.forename: Jette G
authors.initials: JG
authors.lastname: Hemmingsen
authors.forename: Martin
authors.initials: M
authors.lastname: Roursgaard
authors.forename: Dorina Gabriela
authors.initials: DG
authors.lastname: Karotki
authors.forename: Peter
authors.initials: P
authors.lastname: Møller
mesh_terms: D000818:Animals; D015415:Biomarkers; D014408:Biomarkers, Tumor / Q000652:urine*; D002446:Celiac Disease / Q000652:urine*; D004249:DNA Damage; D045647:DNA Glycosylases / Q000378:metabolism; D003704:Dementia / Q000652:urine*; D006801:Humans; D009369:Neoplasms / Q000652:urine*; D010084:Oxidation-Reduction; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human