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Altered apoptotic profiles in irradiated patients with increased toxicity
- Source :
- International journal of radiation oncology, biology, physics. 45(3)
- Publication Year :
- 1999
-
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 PACScan 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. (C) 1999 Elsevier Science Inc.
- Subjects :
- Adult
CD4-Positive T-Lymphocytes
Cancer Research
Pathology
medicine.medical_specialty
Apoptosis
DNA Fragmentation
CD8-Positive T-Lymphocytes
Radiation Tolerance
Andrology
Cohort Studies
chemistry.chemical_compound
Ataxia Telangiectasia
medicine
Humans
Radiology, Nuclear Medicine and imaging
Radiosensitivity
Propidium iodide
Prospective cohort study
Aged
Retrospective Studies
Aged, 80 and over
Radiation
business.industry
Radiology, Nuclear Medicine & Medical Imaging
Homozygote
Becton dickinson
Cancer
DNA
Middle Aged
medicine.disease
Oncology
chemistry
Ataxia-telangiectasia
Toxicity
business
Subjects
Details
- ISSN :
- 03603016
- Volume :
- 45
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- International journal of radiation oncology, biology, physics
- Accession number :
- edsair.doi.dedup.....6e9789b74f9dd9e1d3372c7bd7db92f7