title: Age-dependent changes in DNA repair in radiation-exposed mice.
abstract: Ionizing radiation (IR) is a well-known human carcinogen. Young and adult individuals are known to respond to radiation in a different manner. In this study, we analyzed changes in the spleen of juvenile (two-week-old), adult (two-month-old) and old (18-month-old) C57BL/6 male mice subjected to a whole-body exposure to 1 Gy of X rays. We measured the number of γ-H2AX foci and ATM protein levels as a reflection of the level of DNA double-strand breaks (DSBs), and found that old animals had a high frequency of occurrence of noninduced DSBs. Exposure to X rays resulted in a rapid increase in the number of DSBs in juvenile and adult animals at 6 h postirradiation followed by a return to preirradiated DSB values at 96 h postirradiation. No changes were observed in old animals. The analysis of the levels of proteins involved in DNA damage base excision and mismatch repair pathways, including KU70, RAD51, POL β, POL δ, POL ε, APE1 and MSH2 showed substantial age-dependent radiation-induced differences. Finally, we demonstrated that old animals had a higher background level of cell apoptosis compared to younger animals, but in contrast to younger animals, old animals were not able to commit spleen cells to apoptosis after being irradiated. Thus, spleen cells of old mice have a high level of spontaneous DNA damage, but they are not able to deal with additional radiation-induced damage as efficiently as younger animals, substantiating age-depending differences in radiation-induced DNA damage and repair response and its outcomes.
authors.affiliation: a  Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, Canada.
authors.forename: Igor P
authors.initials: IP
authors.lastname: Kovalchuk
authors.forename: Andrey
authors.initials: A
authors.lastname: Golubov
authors.forename: Igor V
authors.initials: IV
authors.lastname: Koturbash
authors.forename: Kristy
authors.initials: K
authors.lastname: Kutanzi
authors.forename: Olga A
authors.initials: OA
authors.lastname: Martin
authors.forename: Olga
authors.initials: O
authors.lastname: Kovalchuk
mesh_terms: D000375:Aging / Q000235:genetics* / Q000528:radiation effects*; D000818:Animals; D004249:DNA Damage; D059766:DNA End-Joining Repair / Q000502:physiology / Q000528:radiation effects; D004260:DNA Repair / Q000502:physiology* / Q000528:radiation effects*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D059765:Homologous Recombination / Q000502:physiology / Q000528:radiation effects; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000378:metabolism / Q000528:radiation effects
chemical_list: D006657:Histones; C475961:gamma-H2AX protein, mouse; D004259:DNA-Directed DNA Polymerase