Oxidative damage to DNA during aging: 8-hydroxy-2'-deoxyguanosine in rat organ DNA and urine.
Open accessAbstract
Oxidative damage to DNA is shown to be extensive and could be a major cause of the physiological changes associated with aging and the degenerative diseases related to aging such as cancer. The oxidized nucleoside, 8-hydroxy-2'-deoxyguanosine (oh8dG), one of the approximately 20 known oxidative DNA damage products, has been measured in DNA isolated from various organs of Fischer 344 rats of different ages. oh8dG was present in the DNA isolated from all the organs studied: liver, brain, kidney, intestine, and testes. Steady-state levels of oh8dG ranged from 8 to 73 residues per 10(6) deoxyguanosine residues or 0.2-2.0 x 10(5) residues per cell. Levels of oh8dG in DNA increased with age in liver, kidney, and intestine but remained unchanged in brain and testes. The urinary excretion of oh8dG, which presumably reflects its repair from DNA by nuclease activity, decreased with age from 481 to 165 pmol per kg of body weight per day for urine obtained from 2-month- and 25-month-old rats, respectively. 8-Hydroxyguanine, the proposed repair product of a glycosylase activity, was also assayed in the urine. We estimate approximately 9 x 10(4) oxidative hits to DNA per cell per day in the rat. The results suggest that the age-dependent accumulation of oh8dG residues observed in DNA from liver, kidney, and intestine is principally due to the slow loss of DNA nuclease activity; however, an increase in the rate of oxidative DNA damage cannot be ruled out.
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Mitochondrial proteins are also subject to attack by ROS.
“Mitochondrial proteins are also subject to attack by ROS (88, 121, 157, 257, 318).”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [121]
Peroxides produced by mitochondria can create nonenzymatic shunts in the TCA cycle.
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From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [121]
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- Authors
- Fraga, C. G., Shigenaga, M. K., Park, J. W., Degan, P., & Ames, B. N.
- Affiliations
- University of California, Berkeley (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1990-06
- Volume
- 87
- Issue
- 12
- Pages
- 4533-4537
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC54150
- OpenAlex
- W2087249338
- Cited by
- 1,106
- References
- 42
- Citations by year
- 2026: 3 · 2025: 16 · 2024: 11 · 2023: 14 · 2022: 19 · 2021: 18 · 2020: 30 · 2019: 16 · 2018: 17 · 2017: 22 · 2016: 32 · 2015: 33 · 2014: 34 · 2013: 32 · 2012: 30
- FWCI
- 23.21
- 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 Institutes of Health (5r35ca039910-14)
- National Institute on Aging (AG 05489-01)
- National Cancer Institute (CA399 10)
- National Institute of Environmental Health Sciences (ES01896, P30ES001896)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Keywords
- oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine, aging, 8-oxoguanine, urinary excretion, DNA nuclease activity, DNA repair, liver, kidney, intestine, F344 rats, age-related degenerative diseases
- MeSH terms
- 8-Hydroxy-2'-Deoxyguanosine, Aging, Animals, Deoxyguanosine, DNA, DNA Damage, Guanine, Male, Organ Specificity, Oxidation-Reduction, Rats, Inbred F344, Rats
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