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首页> 外文期刊>Radiotherapy and oncology: Journal of the European Society for Therapeutic Radiology and Oncology >Individual differences in chromosomal aberrations after in vitro irradiation of cells from healthy individuals, cancer and cancer susceptibility syndrome patients.
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Individual differences in chromosomal aberrations after in vitro irradiation of cells from healthy individuals, cancer and cancer susceptibility syndrome patients.

机译：健康人，癌症和癌症易感综合症患者细胞体外照射后的染色体畸变个体差异。

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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.
机译：背景：正常组织的放射敏感性是与放射治疗（RT）相关的副作用的关键因素。在这里，我们报告使用三色荧光原位杂交作为放射敏感性的量度，对来自222个不同个体的256,679个中期的自发和体外照射诱导的染色体畸变进行了分析。材料与方法：样品分为以下6组：（1）健康个体，（2）放疗前的癌症患者，（3）RT治疗的癌症患者，（4）杂合子或（5）突变纯合子共济失调毛细血管扩张突变（ATM）基因或奈梅亨破坏综合症（NBS1）基因中的过敏症和（6）过敏症患者（异常值）。结果：所有检查组均采用染色体畸变数的正态分布，以每个中期的断裂数（B / m）表示。对照组的平均值为0.40B / m（SD +/- 0.07）。与175名未暴露（0.50 +/- 0.12B / m）和预暴露（0.50 +/- 0.16B / m）癌症患者的平均破损率相比，该值更低。来自分析过的癌症患者的十九个中期扩散具有大量的染色体畸变（1.04 +/- 0.29B / m），并被指定为一个单独的超敏亚组（异常值）。该组的像差频率与ATM或NBS1杂合子的像差频率相当（0.86 +/- 0.26B / m）。在ATM和NBS1纯合患者中，畸变发生率最高（2.23 +/- 1.03B / m）。结论：分析组中断裂事件的发生频率导致正态分布，均值和宽度各异，为每组定义了特征敏感性模式。在与RT相关的癌症患者组中，那些患有癌症的患者中，大约三分之一的正态分布样本被确定为敏感的，这是由高于正常个体的高斯99％置信区间的诱发像差​​定义分配。这些样本中约有5％位于RT相关组的正态分布的99％置信区间之外。这些具有较高染色体破损率的异常值表明，一类独特的超敏个体易受染色体损伤，并可能直接增加与放射治疗相关并发症的风险。

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