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- Title
Age-Related Loss of the DNA Repair Response Following Exposure to Oxidative Stress.
- Authors
Cabelof, Diane C.; Raffoul, Julian J.; Ge, Yubin; Van Remmen, Holly; Matherly, Larry H.; Heydari, Ahmad R.
- Abstract
Young (4- to 6-month-old) and aged (24- to 28-month-old) mice were exposed to 2-nitropropane (2-NP), a DNA oxidizing agent, and the ability to induce DNA polymerase β (β-pol) and AP endonuclease (APE) was determined. In contrast to the inducibility of these gene products in response to oxidative damage in young mice, aged mice showed a lack of inducibility of β-pol and APE. APE protein level and endonuclease activity were both reduced 40% (p < .01) in response to 2-NP. Accordingly, the accumulation of DNA repair intermediates in response to 2-NP differed with age. Young animals accumulated 3prime;OH-containing DNA strand breaks, whereas the aged animals did not. A role for p53 in the difference in DNA damage response with age is suggested by the observation that the accumulation of p53 protein in response to DNA damage in young animals was absent in the aged animals. Our results are consistent with a reduced ability to process DNA damage with age.
- Subjects
LABORATORY mice; NITROPROPANE; ENDONUCLEASES; DNA damage; BIOCHEMICAL genetics
- Publication
Journals of Gerontology Series A: Biological Sciences & Medical Sciences, 2006, Vol 61, Issue 5, p427
- ISSN
1079-5006
- Publication type
Article
- DOI
10.1093/gerona/61.5.427