Abstract | BACKGROUND: Radiosensitivity of normal tissue is a crucial factor of radiotherapy (RT)-related side effects. Here, we report the analysis of spontaneous and in vitro irradiation-induced chromosomal aberrations in 256,679 metaphases from 222 different individuals using three-color fluorescence in situ hybridization as a measure of radiosensitivity. MATERIALS AND METHODS: Samples were categorized into the following 6 groups: (1) healthy individuals, (2) cancer patients prior to radiotherapy, (3) RT-treated cancer patients, (4) individuals heterozygous or (5) homozygous for a mutation in the ataxia telangiectasia mutated (ATM) gene or in the Nijmegen breakage syndrome (NBS1) gene and (6) hypersensitive patients (outliers). RESULTS: A normal distribution of the number of chromosomal aberrations, measured as breaks per metaphase (B/m), was adopted for all examined groups. The mean value of the control group was 0.40B/m (SD+/-0.07). This value was lower compared to the mean breakage rate from 175 non-exposed (0.50+/-0.12B/m) and pre-exposed (0.50+/-0.16B/m) cancer patients. Nineteen of the metaphase spreads from the analyzed cancer patients had a high number of chromosomal aberrations (1.04+/-0.29B/m) and were designated as a separate hypersensitive subgroup (outliers). The aberration frequency of this group was comparable to those of ATM or NBS1 heterozygotes (0.86+/-0.26B/m). The highest incidence of aberrations was observed in ATM and NBS1 homozygous patients (2.23+/-1.03B/m). CONCLUSION: The frequency of break events in the analyzed groups resulted in a normal distribution with varying means and broadnesses defining a characteristic sensitivity pattern for each group. In the RT-relevant group of cancer patients, those patients who have cancer, about one-third of the normally distributed samples were determined to be sensitive as defined by the number of induced aberrations higher than the 99% confidence interval of the normal individual's Gaussian distribution. About 5% of these samples were outside of the 99% confidence interval for the RT-relevant group's normal distribution. These outliers with higher chromosomal breakage rates suggest a unique class of hypersensitive individuals that are susceptible to chromosomal damage and may be directly associated with an increased risk to suffer from radiotherapy-related complications.
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Authors | Luitpold V R Distel, Susann Neubauer, Ulrike Keller, Carl N Sprung, Rolf Sauer, Gerhard G Grabenbauer |
Journal | Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
(Radiother Oncol)
Vol. 81
Issue 3
Pg. 257-63
(Dec 2006)
ISSN: 0167-8140 [Print] Ireland |
PMID | 17113667
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cell Cycle Proteins
- DNA-Binding Proteins
- NBN protein, human
- Nuclear Proteins
- Tumor Suppressor Proteins
- ATM protein, human
- Ataxia Telangiectasia Mutated Proteins
- Protein Serine-Threonine Kinases
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Topics |
- Ataxia Telangiectasia Mutated Proteins
- Cell Cycle Proteins
(genetics)
- Cells, Cultured
(radiation effects)
- Chromosome Aberrations
- Chromosomes, Human
(genetics)
- DNA-Binding Proteins
(genetics)
- Disease Susceptibility
- Female
- Genotype
- Heterozygote
- Homozygote
- Humans
- In Situ Hybridization, Fluorescence
- Male
- Metaphase
- Neoplasms
(genetics, pathology, radiotherapy)
- Nuclear Proteins
(genetics)
- Protein Serine-Threonine Kinases
(genetics)
- Radiation Tolerance
- Syndrome
- Tumor Suppressor Proteins
(genetics)
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