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Age-Related Loss of the DNA Repair Response Following Exposure to Oxidative Stress

¹ Developmental Therapeutics Program and ² Department of Nutrition and Food Science, Wayne State University, Detroit, Michigan.
³ Department of Cellular and Structural Biology and the Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio.
⁴ South Texas Veterans Health Care System, San Antonio.
⁵ Department of Pharmacology, Wayne State University School of Medicine, Detroit.

Address correspondence to Diane C. Cabelof, PhD, Barbara Ann Karmanos Cancer Institute, 110 East Warren Avenue, Wayne State University School of Medicine, Detroit, MI 48201. E-mail: d.cabelof{at}wayne.edu

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 ß (ß-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 ß-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 3'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.

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