title: High levels of delayed radiation-induced apoptosis observed in lymphoblastoid cell lines from ataxia-telangiectasia patients.
abstract: 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.
authors.affiliation: Division of Radiation Medicine, Biosciences Department, Paul Scherrer Institute, Villigen-PSI, Switzerland.
authors.forename: Y Q
authors.initials: YQ
authors.lastname: Shi
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: O
authors.initials: O
authors.lastname: Sanal
authors.forename: I
authors.initials: I
authors.lastname: Tezcan
authors.forename: G C
authors.initials: GC
authors.lastname: Emery
authors.forename: H
authors.initials: H
authors.lastname: Blattmann
authors.forename: N E
authors.initials: NE
authors.lastname: Crompton
mesh_terms: 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