Individual differences in chromosomal aberrations after in vitro irradiation of cells from healthy individuals, cancer and cancer susceptibility syndrome patients
Individual differences in chromosomal aberrations after in vitro irradiation of cells from healthy individuals, cancer and cancer susceptibility syndrome patients
复制标题
DOI：
10.1016/j.radonc.2006.10.012
复制
发表时间：
2006-12-01
影响因子：
5.7
通讯作者：
Grabenbauer, Gerhard G.
中科院分区：
文献类型：
--
作者：
Distel, Luitpold V. R.;Neubauer, Susann;Grabenbauer, Gerhard G.
背景：正常组织的放射敏感性是放射治疗（RT）相关副作用的关键因素。在这里，我们报告了使用三色荧光原位杂交作为放射敏感性的测量方法对来自222个不同个体的256，679个中期分裂相的自发和体外辐射诱导的染色体畸变进行分析。材料和方法：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）共济失调毛细血管扩张突变（ATM）基因或奈梅亨断裂综合征（NBS1）基因突变的杂合或（5）纯合个体，以及（6）结果：所有受检组的染色体畸变数均呈正态分布，以每个中期分裂相的断裂数（B/m）表示。对照组的平均值为0.40 B/m（SD +/-0.07）。该值低于175名未暴露（0.50 +/-0.12 B/m）和暴露前（0.50 +/-0.16 B/m）癌症患者的平均断裂率。来自分析的癌症患者的19份中期涂片具有大量染色体畸变（1.04 +/-0.29 B/m），并被指定为单独的超敏亚组（离群值）。这组的畸变频率与ATM或NBS1杂合子的畸变频率（0.86 ± 0.26 B/m）相当。在ATM和NBS1纯合子患者中观察到最高的畸变发生率（2.23 +/-1.03 B/m）。结论：在分析的组中，断裂事件的频率导致正态分布，具有不同的平均值和宽度，定义了每组的特征敏感性模式。在癌症患者的RT相关组中，即那些患有癌症的患者中，约三分之一的正态分布样本被确定为敏感的，如由高于正常个体高斯分布的99%置信区间的诱导畸变的数量所定义的。这些样本中约有5%超出RT相关组正态分布的99%置信区间。这些具有较高染色体断裂率的异常值表明了一类独特的过敏个体，其对染色体损伤敏感，并且可能与遭受放射治疗相关并发症的风险增加直接相关。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
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 0.40 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. (c) 2006 Elsevier Ireland Ltd. All rights reserved.