Variation in radiation-induced apoptosis in ataxia telangiectasia lymphoblastoid cell lines.
OBJECTIVE
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.


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.
DNA Repair Group, International Agency for Research on Cancer, 150 cours Albert Thomas, F-69372 Lyon Cedex 08, France.
M
M
Fernet
S
S
Angele
T
T
Dörk
J
J
Hall
D017209:Apoptosis; D001260:Ataxia Telangiectasia / Q000473:pathology*; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000378:metabolism; D002469:Cell Separation; D003593:Cytoplasm / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D016193:G1 Phase; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000473:pathology*; D010641:Phenotype; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016159:Tumor Suppressor Protein p53; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases