Individual differences in chromosomal aberrations after in vitro irradiation of cells from healthy individuals, cancer and cancer susceptibility syndrome patients
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 hybridizat...
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Veröffentlicht in: | Radiotherapy and oncology 2006-12, Vol.81 (3), p.257-263 |
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Zusammenfassung: | 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.
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).
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).
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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ISSN: | 0167-8140 1879-0887 |
DOI: | 10.1016/j.radonc.2006.10.012 |