High levels of delayed radiation-induced apoptosis observed in lymphoblastoid cell lines from ataxia-telangiectasia patients

Purpose: Cells front ataxia-telangiectasia (A-T) patients are extremely sen sitive to radiation but display decreased apoptosis, as measured during the first 3 days following radiation. To explain this apparent contradiction, we examined apoptosis in normal and A-T cells at late time points following radiation, under the assumption that radiation-induced apoptosis is delaye d in the A-T cells. Methods and Materials: Blood cells and lymphoblastoid cell lines from A-T p atients, as well as healthy donors, were irradiated with X-rays. Apoptosis was measured at different time points (up to 7 and 30 days for lymphocytes and lymphoblastoid cells, respectively) using a flow cytometric method base d on the reduction of intracellular DNA content (sub-G1 population). Results: Compared to normal cells, CD4 and CD8 A-T lymphocytes displayed co nstantly reduced levels of radiation-induced apoptosis for up to 7 days aft er treatment. A-T lymphoblastoid cells, however, displayed a delayed and pr olonged apoptosis. Conclusion: A-T lymphoblastoid cells show high levels of delayed radiation- induced apoptosis, which may contribute to the high cellular radiosensitivi ty displayed by the A-T phenotype, ATR I (the gene mutated in A-T) plays di fferent roles in the apoptotic response to ionizing radiation in quiescent lymphocytes and proliferative lymphoblastoid cells. (C) 2001 Elsevier Scien ce inc.