Article (Scientific journals)
Altered apoptotic profiles in irradiated patients with increased toxicity.
Crompton, Nigel; Miralbell, Raymond; Rutz, Hans-Peter et al.
1999In International Journal of Radiation, Oncology, Biology, Physics, 45 (3), p. 707-714
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Keywords :
Normal tissue toxicity; Radiation-induced apoptosis; Ataxia telangiectasia,; Concomitant chemotherapy; Lymphocytes.
Abstract :
[en] 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 (21.8 s) than average age-matched donors. A cohort of 9 ataxia telangiectasia homozygotes displayed even less apoptosis (23.6 s). 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. © 1999 Elsevier Science Inc.
Disciplines :
Hematology
Oncology
Author, co-author :
Crompton, Nigel;  Paul Scherrer Institute (PSI) > Radiation Medicine, Life Sciences > Switzerland
Miralbell, Raymond;  Hôpital Cantonal Universitaire de Genève (HCUG) > Radiation Oncology > Geneva, Switzerland
Rutz, Hans-Peter;  Kantonsspital Winterthur > Radiation Oncology > Switzerland
Ersoy, Fügen;  Hacettepe Children’s Hospital > Immunology Division > Ankara, Turkey
Sanal, Özden;  Hacettepe Children’s Hospital > Immunology Division > Ankara, Turkey
Wellmann, Danielle;  Hôpital Cantonal de Fribourg > Radiation Oncology > Switzerland
Bieri, Sabine;  Ospedale San Giovanni > Radiation Oncology > Bellinzona, Switzerland
Emery, Gillian;  Paul Scherrer Institute (PSI) > Radiation Medicine, Life Sciences > Switzerland
Shi, Yu-Quan;  Paul Scherrer Institute (PSI) > Radiation Medicine, Life Sciences Department > Switzerland
COUCKE, Philippe  ;  Centre Hospitalier Universitaire Vaudois (CHUV)
OzsahinBlattmann
Ozsahin
Language :
English
Title :
Altered apoptotic profiles in irradiated patients with increased toxicity.
Publication date :
1999
Journal title :
International Journal of Radiation, Oncology, Biology, Physics
ISSN :
0360-3016
eISSN :
1879-355X
Publisher :
Elsevier Science, Tarrytown, United States - New York
Volume :
45
Issue :
3
Pages :
707-714
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 15 July 2009

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