Elevated frequency of p53-independent apoptosis after irradiation increases levels of DNA breaks in ataxia telangiectasia lymphoblasts.
Ataxia telangiectasia is a recessive generic disease featuring cerebellar degeneration, developmental abnormalities, high cancer risk, immunodeficiency, and radiosensitivity. Increased levels of unrepaired DNA breaks have been observed in irradiated ataxia telangiectasia cells compared to normal cells but no specific DNA break rejoining rate deficiency has been defined. Alterations in radiation-induced p53-dependent apoptosis have been reported for ataxia telangiectasia cells. This study investigated the radiation response of ataxia telangiectasia lymphoblastoid cells using the comet assay and uncovered a new feature of this technique, namely its capacity to preferentially detect living cells. It is shown here that early after exposure to gamma-rays, ataxia telangiectasia lymphoblasts exhibit an elevated frequency of cells committed to die via apoptosis. The observed apoptosis, which is likely to be independent of p53, leads to a higher number of DNA breaks during the first 3 h post irradiation in ataxia telangiectasia cells, relative to controls. Apart from cells undergoing apoptosis, ataxia telangiectasia lymphoblasts have an identical capacity to rejoin radiation-induced DNA breaks as controls. Results suggest that p53-independent apoptosis may contribute to the radiosensitivity and the immune defects of ataxia telangiectasia patients.
Humar
B
B
Department of Research, University Hospital, Basel, Switzerland.
Müller
H
H
Scott
R J
RJ
D000328:Adult; D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects*; D001260:Ataxia Telangiectasia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002467:Cell Nucleus / Q000528:radiation effects; D004247:DNA / Q000378:metabolism* / Q000528:radiation effects*; D004249:DNA Damage; D004854:Herpesvirus 4, Human; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism* / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D016159:Tumor Suppressor Protein p53; D004247:DNA