title: Induction and persistence of radiation-induced DNA damage is more pronounced in young animals than in old animals.
abstract: Younger individuals are more prone to develop cancer upon ionizing radiation (IR) exposure. Radiation-induced tumors are associated with inefficient repair of IR-induced DNA damage and genome instability. Phosphorylation of histone H2AX (γ-H2AX) is the initial event in repair of IR-induced DNA damage on the chromatin flanking the DNA strand breaks. This step is crucially important for the repair of DNA strand breaks and for the maintenance of genome stability. We studied the molecular underpinnings of the age-related IR effects using an animal model. By assaying for IR-induced γ-H2AX foci we analyzed the induction and repair of the DNA strand breaks in spleen, thymus, liver, lung, kidney, cerebellum, hippocampus, frontal cortex and olfactory bulb of 7, 14, 24, 30 and 45 days old male and female mice as a function of age. We demonstrate that tissues of younger animals are much more susceptible to IR-induced DNA damage. Younger animals exhibited higher levels of γ-H2AX formation which partially correlated with cellular proliferation and expression of DNA repair proteins. Induction and persistence of γ-H2AX foci was the highest in lymphoid organs (thymus and spleen) of 7 and 14 day old mice. The lowest focal induction was seen in lung and brain of young animals. The mechanisms of cell and tissue-specificity of in vivo IR responses need to be further dissected. This study provides a roadmap for the future analyses of DNA damage and repair induction in young individuals.
authors.affiliation: Department of Biological Sciences, University of Lethbridge, Lethbridge, AB, T1K 3M4 Canada.
authors.forename: Darryl
authors.initials: D
authors.lastname: Hudson
authors.forename: Igor
authors.initials: I
authors.lastname: Kovalchuk
authors.forename: Igor
authors.initials: I
authors.lastname: Koturbash
authors.forename: Bryan
authors.initials: B
authors.lastname: Kolb
authors.forename: Olga A
authors.initials: OA
authors.lastname: Martin
authors.forename: Olga
authors.initials: O
authors.lastname: Kovalchuk
mesh_terms: D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000473:pathology / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D002648:Child; D004247:DNA / Q000528:radiation effects*; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D010766:Phosphorylation; D011839:Radiation, Ionizing
chemical_list: D006657:Histones; C475961:gamma-H2AX protein, mouse; D004247:DNA