title: Age-dependent decline in rejoining of X-ray-induced DNA double-strand breaks in normal human lymphocytes.
abstract: Unstimulated human peripheral blood lymphocytes (HPBL), separated by density centrifugation from anticoagulated whole blood, were X-irradiated (30 Gy) on ice and incubated in medium at 37 degrees C for repair times of 15, 30, and 120 min. Blood donors were 18 normotensive, non-smoking Caucasians aged 23-78, free from overt pathology and not taking any medications. Neutral filter elution was used to assay DNA double-strand break (DSB) induction and completeness of DSB rejoining (plus rejoining of any X-ray-induced alkali-labile sites converted to DSBs in vitro at pH 9.6). After 30 or 120 min repair incubation, the percentage of DSBs rejoined by cells from older donors (aged 66-78 years) was less than half the percentage of DSBs rejoined by cells from younger donors (aged 23-39 and 42-57). When data from the 3 age groups were pooled, the age-related decline in percent DSBs rejoined was significant for repair times 30 min (r = -0.63, p less than 0.005) and 120 min (r = -0.64, p less than 0.005) but not for 15 min (r = -0.04). These age-related declines were observed even though DNA from older donors sustained fewer strand breaks as demonstrated by the negative correlation between donor age and DSB induction (r = -0.65, p less than 0.005). These results suggest that the efficacy of X-ray-induced DSB repair diminishes with in vivo age in unstimulated HPBL.
authors.affiliation: Department of Radiation Oncology, State University of New York Health Science Center, Brooklyn 11203.
authors.forename: P J
authors.initials: PJ
authors.lastname: Mayer
authors.forename: C S
authors.initials: CS
authors.lastname: Lange
authors.forename: M O
authors.initials: MO
authors.lastname: Bradley
authors.forename: W W
authors.initials: WW
authors.lastname: Nichols
mesh_terms: D000375:Aging; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000528:radiation effects; D014965:X-Rays
chemical_list: D004247:DNA