title: [Changes in the radiation-induced apoptotic response in homozygotes and heterozygotes for the ataxia-telangiectasia gene].
abstract: Ataxia-telangiectasia is a progressive recessive disease featuring neurodegeneration, immunodeficiency, chromosomal instability, radiation hypersensitivity and increased predisposition to cancer. Impaired induction of the tumor suppressor protein p53 after gamma-irradiation was recently reported. All together these characteristics may be compatible with an inability to correctly regulate the apoptotic pathway of cell death in this syndrome. We show here that lymphocyte cultures from AT patients are characterized by a 3 times more elevated spontaneous level of apoptotic cells compared to normal ones. In spite of this, 24 h after exposure to gamma-irradiation (5 to 10 Gy), AT lymphocytes show a dramatically reduced capacity to undergo apoptosis compared to normal cells. We obtained similar results on EBV-transformed lymphoblasts. Interestingly, lymphoblasts from obligate heterozygous for the AT mutation(s) show the same features as AT lymphoblasts, i.e. an elevated frequency of spontaneous and a reduced level of radio-induced apoptotic figures in comparison to normal cultured cells. In conclusion, we show here, for the first time, that mutation(s) in AT gene(s) results in an impaired ability to correctly regulate the apoptotic pathway of cell death.
authors.affiliation: URA 1292 du CNRS, Institut Curie-Biologie, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Duchaud
authors.forename: A
authors.initials: A
authors.lastname: Ridet
authors.forename: Y
authors.initials: Y
authors.lastname: Delic
authors.forename: E
authors.initials: E
authors.lastname: Cundari
authors.forename: E
authors.initials: E
authors.lastname: Moustacchi
authors.forename: F
authors.initials: F
authors.lastname: Rosselli
mesh_terms: D017209:Apoptosis / Q000528:radiation effects*; D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000503:physiopathology; D002455:Cell Division / Q000528:radiation effects; D003037:Cobalt Radioisotopes / Q000494:pharmacology; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000502:physiology
chemical_list: D003037:Cobalt Radioisotopes
vernacular_title: Altération de la réponse apoptotique radio-induite chez des homozygotes et des hétérozygotes pour l'ataxie-télangiectasie.