Fibroblasts from Ataxia Telangiectasia (AT) and AT Heterozygotes Show an Enhanced Level of Residual DNA Double-strand Breaks after Low Dose-rate γ-irradiation as Assayed by Pulsed Field Gel Electrophoresis

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Abstract
Skin fibroblasts from ataxia telangiectasia (AT) patients, obligate AT heterozygotes (ATH) and normal individuals were studied for colony-forming ability and repair of DNA double-strand breaks (dsb) after γ-irradiation. AT cells were three to four times more radiosensitive than normal cells at high and low dose-rate exposures; ATH cells, however, showed a marginally increased radiosensitivity after high dose-rate γ-irradiation and an intermediate response after low dose-rate exposure. The repair of DNA dsb was studied by pulsed field gel electrophoresis. After high dose-rate γ-irradiation the repair time constant (t1/2) was around 1 h for normal, ATH and AT cells. After low dose-rate γ-irradiation the fraction of residual dsb was 1·4% for normal, 2·1% for ATH and 5·2% for AT cells, demonstrating a deficiency in the repair of a small fraction of dsb in AT. Thus the fraction of residual dsb after low dose-rate exposure was not only four times higher in AT than in normal cells, but was also significantly increased in ATH compared to normal cells.