Fibroblasts from ataxia telangiectasia (AT) and AT heterozygotes show an enhanced level of residual DNA double-strand breaks after low dose-rate gamma-irradiation as assayed by pulsed field gel electrophoresis.
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 gamma-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 gamma-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 gamma-irradiation the repair time constant (t1/2) was around 1 h for normal, ATH and AT cells. After low dose-rate gamma-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.
Biomedical Physics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
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Blöcher
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Sigut
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Hannan
D001260:Ataxia Telangiectasia / Q000235:genetics / Q000473:pathology*; D002470:Cell Survival / Q000528:radiation effects; D003037:Cobalt Radioisotopes; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D016521:Electrophoresis, Gel, Pulsed-Field; D005347:Fibroblasts / Q000528:radiation effects; D005720:Gamma Rays; D006579:Heterozygote; D006801:Humans
D003037:Cobalt Radioisotopes; D004247:DNA