- 作者：Luitpold V.R. Distel ; Susann Neubauer ; Ulrike Keller ; Carl N. Sprung ; Rolf Sauer ; Gerhard G. Grabenbauer
- 关键词：Chromosomal aberrations ; Cancer patients ; ATM ; NBS1 ; Individual sensitivity ; Cancer risk
- 刊名：Radiotherapy and Oncology
- 出版年：2006
- 期刊代码：231_01678140
- 类别：med
- 出版时间：December 2006
- 卷：81
- 期：3
- 页码：257-263
- 文件大小：428 K
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 0.40 B/m (SD ± 0.07). This value was lower compared to the mean breakage rate from 175 non-exposed (0.50 ± 0.12 B/m) and pre-exposed (0.50 ± 0.16 B/m) cancer patients. Nineteen of the metaphase spreads from the analyzed cancer patients had a high number of chromosomal aberrations (1.04 ± 0.29 B/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 ± 0.26 B/m). The highest incidence of aberrations was observed in ATM and NBS1 homozygous patients (2.23 ± 1.03 B/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.