Urinary 8-hydroxy-2'-deoxyguanosine as a biological marker of in vivo oxidative DNA damage.
Open accessAbstract
DNA is subject to constant oxidative damage from endogenous oxidants. The oxidized DNA is continuously repaired and the oxidized bases are excreted in the urine. A simple routine analytical procedure is described for urinary 8-hydroxy-2'-deoxyguanosine, an oxidative DNA damage adduct, as an indicator of oxidative damage in humans and rodents. This adduct was purified from human urine and characterized. The described assay employs a series of solid-phase extraction steps that separate 8-hydroxy-2'-deoxyguanosine from other urinary constituents, followed by analysis by gradient reversed-phase HPLC coupled to a dual-electrode high-efficiency electrochemical detection system. Analysis of urine from three species by this method indicates that mice excrete approximately 3.3-fold more 8-hydroxy-2'-deoxyguanosine than humans (582 vs. 178 residues per cell per day), a result that supports the proposal that oxidative damage to DNA increases in proportion to species-specific basal metabolic rates.
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The prevalence of the G:C→T:A transversion possibly reflects the mutagenicity of guanine oxidative products produced in culture under ambient oxygen concentrations.
“The most prevalent mutation type was the G:C → T:A transversion (Fig. 2 A ), possibly reflecting the mutagenicity of guanine oxidative products produced in culture under ambient oxygen concentrations (29 -31).”
From Why Cockayne syndrome patients do not get cancer despite their DNA repair deficiency (2016) · cites this paper as [30]
The Discussion (page not available in our copy) says that oxidized guanine in DNA can cause mispairing, suggesting that it may be mutagenic. It does not identify a G:C→T:A transversion or say that the oxidative products arise in culture under ambient oxygen concentrations. (LLM, conf=0.87)
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- Authors
- Shigenaga, M. K., Gimeno, C. J., & Ames, B. N.
- Affiliations
- University of California, Berkeley (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1989-12
- Volume
- 86
- Issue
- 24
- Pages
- 9697-9701
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC298568
- OpenAlex
- W2010597170
- Cited by
- 732
- References
- 0
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 13 · 2023: 11 · 2022: 14 · 2021: 14 · 2020: 17 · 2019: 6 · 2018: 14 · 2017: 7 · 2016: 16 · 2015: 14 · 2014: 21 · 2013: 20 · 2012: 25
- FWCI
- 8.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA399 10)
- National Institute of Environmental Health Sciences (ES01896)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- 8-hydroxy-2'-deoxyguanosine, oxidative DNA damage, urinary biomarkers, DNA adducts, solid-phase extraction, electrochemical detection, HPLC, basal metabolic rate, mice, human
- MeSH terms
- 8-Hydroxy-2'-Deoxyguanosine, Animals, Chromatography, High Pressure Liquid, Deoxyguanosine, DNA Damage, Humans, Oxidation-Reduction, Rats, Inbred F344, Reference Values, Species Specificity, Biomarkers, Mice, Rats
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