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.
Blöcher
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Biomedical Physics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
Sigut
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D
Hannan
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MA
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