Deficient repair of potentially lethal damage in actively growing ataxia telangiectasia cells

The repair of potentially lethal damage after X rays was studied in exponentially growing normal and ataxia telangiectasia (A-T) strains of human fibroblasts. X-ray killing of all normal strains from six healthy persons was enhanced when cells were treated with treated with hypertonic phosphate-buffered saline immediately after irradiation. This treatment is not toxic to unirradiated cells and demonstrates that ordinarily these cells repair potentially lethal damage. The potentially lethal damage in normal cells is repaired within 1 hr. These data with normal human fibroblasts are similar to and consistent with those obtained with V79 Chinese hamster cells [H. Utsumi and M. M. Elkind, Radiat. Res. 77, 346-360 (1979)]. In contrast, all A-T strains from four A-T patients were completely deficient in their ability to repair potentially lethal damage. Treatment with a hypertonic solution after X irradiation is known to increase the frequency of chromosomal aberrations and to enhance cell killing, as though hypertonicity had induced the A-T state in normal cells. Recently, the effects of hypertonicity on DNA synthesis in X-irradiated normal and A-T cells were reported to be similar [R.B. Painter and B.R. Young, Radiat. Res. 92, 552-559 (1982)]. These results support the inference that the increased radiosensitivity of A-T cells can be attributed to some defect in the repair of DNA damage rather than abnormal DNA synthesis following irradiation.