Radiobiology of Ataxia-Telangiectasia

Abstract

The discovery that ataxia-telangiectasia (A-T) patients (Morgan et al., 1968; Gotoff et al., 1967; Cunliffe et al., 1975), as well as cells from these patients (Taylor et al., 1975), are hypersensitive to ionizing radiation (Fig. 1) has sparked an outpouring of research aimed at determining the basis of this radiosensitivity and its relationship to the pathology of the disease. The increased susceptibility of A-T cells to killing by ionizing radiation can largely be correlated with the increased frequency of radiation-induced chromosomal aberrations (Bender et al., 1985, 1988; Higurachi and Conen, 1973; Nagasawa et al., 1985; Natarajan and Meyers, 1979; Taylor, 1982; Zampetti-Bosseler and Scott, 1981); however, the molecular basis of this extraordinary radiosensitivity is still not understood. Many chromatid-type aberrations are observed after irradiation of A-T cells in the G₁ phase of the cell cycle (Bender et al., 1985; Natarajan and Meyers, 1979; Taylor et al., 1976; Taylor, 1978), something almost never seen in normal cells or in cells from patients with other genetic diseases. This suggests that some kind of damage that is always repaired in normal cells before they move into S phase is not repaired in A-T cells. Unfortunately, this is a clue that no one has yet been able to exploit.