DNA-repair and the frequency of chromosome aberration after u.v. and X-ray irradiation was studied on leukocytes from patients with Down's syndrome. The u.v.-induced DNA-repair synthesis was followed by the incorporation of [3H]thymidine in the presence of hydroxyurea. Similar dose-response curves were established for Down's syndrome leukocytes and controls. The cells from patients with Down's syndrome incorporated 70-75% of the activity of control cells at the various doses (32-196 erg/mm.2). This difference was significant for the two highest u.v.-doses (P less than 0-01). The yield of dicentric chromosomes after X-ray exposure (150 rad.) was 35% higher in Down's syndrome leukocytes than in the control cells (P less than 0-001). Combined u.v. and X-ray irradiation caused a twofold increase in the frequency of dicentric chromosomes in control cells, while the increase was only 27% in Down's syndrome leukocytes. This synergistic effect of u.v. and X-ray irradiation on the yield of dicentric chromosomes suggests that healing of X-ray and u.v.-induced DNA lesions may partly utilize the same repair enzymes. The results also indicate that DNA repair mechanisms are impaired in leukocytes from patients with Down's syndrome, which may contribute to the increased incidence of leukemia and the susceptibility to X-ray irradiation in this disorder.
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