Ataxia telangiectasia (AT) is a recessive genetic disease featuring neurodegeneration, immunodeficiency, chromosomal instability, radiation hypersensitivity, and increased predisposition to cancer. Reduced or delayed induction of the tumor suppressor protein p53 after γ-irradiation was reported. These characteristics may be compatible with an inability to correctly regulate apoptosis. We show here that AT lymphocytes and EBV-transformed lymphoblasts demonstrate a significantly higher level of spontaneous apoptosis, whereas ionizing radiation-induced apoptosis is reduced compared to normal cells. However, neither AT nor normal primary fibroblasts undergo apoptosis after irradiation. Consequently, we conclude that the radiosensitivity of the AT cells is not related to an increased apoptotic response. Finally, we show that SV40-transformed AT fibroblasts undergo γ-ray-induced apoptosis, while SV40-transformed normal cells do not. This result raises the question of the physiological relevance of the latter cellular model with respect to the AT phenotype.

1

Supported by the European Economic Community (Brussels), Association pour la Recherche sur le Cancer (Paris), Ligue Nationale Contre le Cancer (Paris), Electricité de France (Paris), and Commissariat à l'Energie Atomique (Paris).

This content is only available via PDF.