High levels of delayed radiation-induced apoptosis observed in lymphoblastoid cell lines from ataxia-telangiectasia patients.
OBJECTIVE
Cells from ataxia-telangiectasia (A-T) patients are extremely sensitive 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 delayed in the A-T cells.


METHODS
Blood cells and lymphoblastoid cell lines from A-T patients, 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 based on the reduction of intracellular DNA content (sub-G1 population).


RESULTS
Compared to normal cells, CD4 and CD8 A-T lymphocytes displayed constantly reduced levels of radiation-induced apoptosis for up to 7 days after treatment. A-T lymphoblastoid cells, however, displayed a delayed and prolonged apoptosis.


CONCLUSIONS
A-T lymphoblastoid cells show high levels of delayed radiation-induced apoptosis, which may contribute to the high cellular radiosensitivity displayed by the A-T phenotype. ATM (the gene mutated in A-T) plays different roles in the apoptotic response to ionizing radiation in quiescent lymphocytes and proliferative lymphoblastoid cells.
Shi
Y Q
YQ
Division of Radiation Medicine, Biosciences Department, Paul Scherrer Institute, Villigen-PSI, Switzerland.
Li
L
L
Sanal
O
O
Tezcan
I
I
Emery
G C
GC
Blattmann
H
H
Crompton
N E
NE
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D001260:Ataxia Telangiectasia / Q000503:physiopathology / Q000532:radiotherapy*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology / Q000528:radiation effects*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology / Q000528:radiation effects*; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D005434:Flow Cytometry; D006801:Humans; D008875:Middle Aged; D011836:Radiation Tolerance / Q000502:physiology; D013997:Time Factors