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Variation in radiation-induced apoptosis in ataxia telangiectasia lymphoblastoid cell lines
1DNA Repair Group, International Agency for Research on Cancer, 150 cours Albert Thomas, F-69372 Lyon Cedex 08, France.
Purpose:
To investigate and compare the ability of Epstein-Barr virus-transformed lymphoblastoid cell lines (LCL) from healthy individuals (normals) and ataxia telangiectasia (A-T) patients to undergo apoptosis after exposure to ionizing radiation.
Materials And Methods:
Four normal and eight A-T LCL were exposed to doses of up to 20 Gy ionizing radiation. Apoptosis induction was studied 24 h after irradiation using three different methods: measurement of caspase-3 activity, PARP-1 cleavage and estimation of the sub-G(1) cell fraction.
Results:
Of the eight A-T LCL tested, all harbouring truncating ATM mutations, five had a higher level of spontaneous apoptosis than the normal LCL as assessed by the sub-G(1) cell fraction. Four of the eight A-T LCLs showed a similar level of radiation-induced apoptosis after exposure to 5 Gy as the normal LCL. The other four A-T LCL showed a greater radiation-induced apoptotic response, as assessed by at least one of the three techniques.
Conclusions:
LCL from A-T patients can undergo ionizing radiation-induced apoptosis in spite of a defect in ATM-p53-dependent signalling pathways. However, the apoptotic response is characterized by a large degree of variability between the A-T cell lines, the causes of which remain to be established.