Altered apoptotic profiles in irradiated patients with increased toxicity

Details

Serval ID
serval:BIB_2EFD48FCC5F0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Altered apoptotic profiles in irradiated patients with increased toxicity
Journal
International Journal of Radiation Oncology, Biology, Physics
Author(s)
Crompton  N. E., Miralbell  R., Rutz  H. P., Ersoy  F., Sanal  O., Wellmann  D., Bieri  S., Coucke  P. A., Emery  G. C., Shi  Y. Q., Blattmann  H., Ozsahin  M.
ISSN
0360-3016
Publication state
Published
Issued date
10/1999
Peer-reviewed
Oui
Volume
45
Number
3
Pages
707-14
Notes
Journal Article --- Old month value: Oct 1
Abstract
PURPOSE: A retrospective study of radiation-induced apoptosis in CD4 and CD8 T-lymphocytes, from 12 cancer patients who displayed enhanced toxicity to radiation therapy and 9 ataxia telangiectasia patients, was performed to test for altered response compared to healthy blood-donors and normal cancer patients. METHODS AND MATERIALS: Three milliliters of heparinized blood from each donor was sent via express post to the Paul Scherrer Institute (PSI) for subsequent examination. The blood was diluted 1:10 in RPMI medium, irradiated with 0-, 2-, or 9-Gy X-rays, and incubated for 48 h. CD4 and CD8 T-lymphocytes were then labeled using FITC-conjugated antibodies, erythrocytes were lysed, and the DNA stained with propidium iodide. Subsequently, cells were analyzed using a Becton Dickinson FACScan flow cytometer. Radiation-induced apoptosis was recognized in leukocytes as reduced DNA content attributed to apoptosis-associated changes in chromatin structure. Apoptosis was confirmed by light microscopy, electron microscopy, and by the use of commercially available apoptosis detection kits (in situ nick translation and Annexin V). Data from hypersensitive individuals were compared to a standard database of 105 healthy blood-donors, and a database of 48 cancer patient blood donors who displayed normal toxicity to radiation therapy. To integrate radiosensitivity results from CD4 and CD8 T-lymphocytes after 2 and 9 Gy, z-score analyses were performed. RESULTS: A cohort of 12 hypersensitive patients was evaluated; 8 showed enhanced early toxicity, 3 showed enhanced late toxicity, and 1 showed both. The cohort displayed less radiation-induced apoptosis (-1.8 sigma) than average age-matched donors. A cohort of 9 ataxia telangiectasia homozygotes displayed even less apoptosis (-3.6 sigma). CONCLUSION: The leukocyte apoptosis assay appears to be a useful predictor of individuals likely to display increased toxicity to radiation therapy; however, validation of this requires a prospective study.
Keywords
Adult Aged Aged, 80 and over *Apoptosis/genetics Ataxia Telangiectasia/blood/genetics CD4-Positive T-Lymphocytes/physiology/*radiation effects CD8-Positive T-Lymphocytes/physiology/*radiation effects Cohort Studies DNA/radiation effects DNA Fragmentation Homozygote Humans Middle Aged *Radiation Tolerance Retrospective Studies
Pubmed
Web of science
Create date
24/01/2008 17:16
Last modification date
20/08/2019 13:13
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