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

C. G. Fraga, M. K. Shigenaga, J. W. Park, P. Degan, B. N. Ames

Research output: Contribution to journalArticlepeer-review

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 (oh 8dG), one of the ~ 20 known oxidative DNA damage products, has been measured in DNA isolated from various organs of Fischer 344 rats of different ages. oh 8dG was present in the DNA isolated from all the organs studied: liver, brain, kidney, intestine, and testes. Steady-state levels of oh 8dG ranged from 8 to 73 residues per 10 6 deoxyguanosine residues or 0.2-2.0 x 10 5 residues per cell. Levels of the oh 8dG in DNA increased with age in liver, kidney, and intestine but remained unchanged in brain and testes. The urinary excretion of oh 8dG, 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 ~ 9 x 10 4 oxidative hits to DNA per cell per day in the rat. The results suggest that the age-dependent accumulation of oh 8dG 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.

Original languageEnglish
Pages (from-to)4533-4537
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number12
DOIs
Publication statusPublished - 1990

Keywords

  • 8-hydroxyguanine
  • cancer
  • endogenous DNA adducts
  • mutation
  • oxygen radicals

ASJC Scopus subject areas

  • General
  • Genetics

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