Full-color painting reveals an excess of radiation-induced dicentrics involving homologous chromosomes.

Full-color painting reveals an excess of radiation-induced dicentrics involving homologous chromosomes.
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全彩绘画揭示了涉及同源染色体的过量辐射诱导双着丝粒。

DOI:
10.1080/09553000500331881
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发表时间:
2005
期刊:
International journal of radiation biology.
影响因子:
--
通讯作者:
Cornforth,M
Cornforth,M
中科院分区:
--
文献类型:
--
作者:
Plan,Y;Hlatky,L;Hahnfeldt,P;Sachs,R;Loucas,B;Cornforth,M

文献摘要

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目的:测定电离辐射诱发的人细胞同源和异源双着丝粒染色体的比例。这一比例受潜在的dna损伤/修复/错误修复过程以及间期核中单个染色体区域的几何形状的影响。材料和方法:24色mFISH(多重荧光原位杂交)用于确定不同剂量的γ射线、α粒子或铁离子在人淋巴细胞或成纤维细胞中产生的单色(同源)双着丝粒和双色(异源)双着丝粒的比例。假设与同源性无关的随机性成立,二倍体人类男性细胞的预期同源:异源比为∼0.024,推导出适用于简单交换的公式,然后通过蒙特卡罗模拟将结果推广到一般情况,其中也考虑了复杂的像差。结果和结论:同源双着丝粒大量存在,三次辐射中每一次发生的概率都小于0.02,所有数据加在一起的概率仅为10−8。总体而言,预计大约有18个同源双着丝粒,但发现了47个,其中11个涉及1号染色体。观察到的过度辐射在稀疏和密集电离辐射中都是相似的。同系物在几何上的接近可能解释了同系物的过剩;在这种情况下,更广泛的统计数据最终应该会揭示出线性能量转移(LET)依赖关系。目前的数据没有排除另一种可能性,那就是同源性相关的错误修复。
Purpose:To determine the ratio of homologous to heterologous dicentric chromosomes induced in human cells by ionizing radiation. This ratio is influenced by, and thus potentially informative about, underlying DNA damage/repair/misrepair processes and also the geometry of individual chromosome domains within the interphase nucleus.Materials and methods:24-color mFISH (multiplex fluorescentin situhybridization) was used to determine the ratio of 1-color (homologous) to 2-color (heterologous) dicentrics produced in human lymphocytes or fibroblasts by γ-rays, alpha particles, or iron ions at various doses. Assuming that randomness independent of homology holds, the expected homologue:heterologue ratio for diploid human male cells is ∼0.024, as shown by deriving a formula applicable to simple interchanges and then extending the result, via Monte Carlo simulation, to the general situation where complex aberrations are also considered.Results and conclusions:There was a substantial excess of homologous dicentrics, with probability of occurrence by chance less than 0.02 for each of the three radiations and only about 10−8for all the data combined. Overall, approximately 18 homologous dicentrics were expected but 47 were found, including 11 involving chromosome 1. Observed excesses were similar for both sparsely and densely ionizing radiations. Geometric proximity of homologues is a possible explanation for the overabundance; in that case more extensive statistics should eventually uncover a linear energy transfer (LET) dependence. An alternative possibility, not ruled out by the present data, is homology-dependent misrepair.