Cited by 1,106Genetics, Aging, and Longevity in Model OrganismsDNA Repair MechanismsCarcinogens and Genotoxicity Assessment

Oxidative damage to DNA during aging: 8-hydroxy-2'-deoxyguanosine in rat organ DNA and urine.

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Fraga, C G, Shigenaga, M K, Park, J W, Degan, P, Ames, B N·1990·Proceedings of the National Academy of Sciences

Abstract

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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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
Published
1990-06
Volume
87
Issue
12
Pages
4533-4537
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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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