Epstein-Barr virus-transformed lymphoblastoid cell lines of ataxia telangiectasia patients are defective in X-ray-induced apoptosis.
OBJECTIVE
To investigate and compare the propensity of Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCL) obtained from unaffected healthy individuals and ataxia telangectasia (A-T) patients to undergo apoptosis after X-ray exposure.


METHODS
The LCL were exposed to 1-4 Gy X-rays at a dose-rate of 1.36 Gy/min. At various post-irradiation times (0, 24, 48 and 72 h) the induction of apoptosis was analysed by: (1) monitoring the formation of high molecular weight (HMW) DNA fragments by field inversion pulse gel electrophoresis (FIGE); and (2) morphological characterization of apoptotic cells after fluorescence staining. In parallel, cell-cycle distribution, monitored by DNA flow cytometry, was investigated in these cells.


RESULTS
The LCL obtained from the A-T homozygotes were resistant to undergoing radiation-induced apoptosis during the observation time used. On the contrary, LCL from unaffected healthy controls displayed significant radiation-induced chromatin fragmentation seen at 48 h and 72 h after irradiation. In these cells, radiation-induced G -arrest (24h post-irradiation) preceded chromatin cleavage. In A-T LCL, the defective G1-arrest was not followed by apoptosis.


CONCLUSIONS
In spite of a defective cell-cycle control, EBV-transformed LCL of A-T patients compared with unaffected healthy controls do not undergo X-ray-induced apoptosis, at least during their first post-irradiation cell cycle.
Swedish Radiation Protection Institute, Stockholm.
A E
AE
Meijer
B
B
Zhivotovsky
R
R
Lewensohn
D017209:Apoptosis / Q000528:radiation effects*; D001260:Ataxia Telangiectasia / Q000235:genetics / Q000473:pathology*; D002453:Cell Cycle / Q000528:radiation effects; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D053938:DNA Fragmentation; D016193:G1 Phase / Q000528:radiation effects; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D008214:Lymphocytes / Q000473:pathology / Q000528:radiation effects; D008970:Molecular Weight; D011836:Radiation Tolerance; D014965:X-Rays