Clustering of radiation-produced breaks along chromosomes: modelling the effects on chromosome aberrations.
Clustering of radiation-produced breaks along chromosomes: modelling the effects on chromosome aberrations.
复制标题
辐射产生的沿染色体断裂的聚集：模拟对染色体畸变的影响。
DOI：
10.1080/095530099139999
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发表时间：
1999
影响因子：
2.6
通讯作者：
Savage,JR
中科院分区：
文献类型：
--
作者：
Sachs,RK;Chen,AM;Simpson,PJ;Hlatky,LR;Hahnfeldt,P;Savage,JR
目的对于高 LET 辐射，甚至可能对于硬 X 射线，DNA 双链断裂 (dsb) 沿着染色体非随机聚集；不成比例地，许多 interdsb 片段小于几个 Mbp（106 个碱基对）。分析了这种 dsb 聚类对染色体畸变的影响。方法假设一个 dsb 聚类内不同 dsb 之间的染色体片段太小而无法在畸变测定中检测到。枚举或蒙特卡罗计算机模拟用于计算许多可观察到的像差模式的相对频率：明显简单或明显复杂。将理论预测与人类成纤维细胞的 X 射线数据进行比较，涉及染色染色体 1、2、4、5、7 或 13。结果和结论令人惊讶的是，神秘的 DSB 多重性并不影响随机断裂和重新连接模型预测的畸变模式的频率比。该模型总体上与许多不同类型像差的当前数据一致，无论 DSB 通常是否出现在神秘星团中。然而，对于 Revell 型交换模型，预测确实取决于聚类配置；随着平均簇多重性的增加，他们逐渐接近断裂与重新连接模型的预测。该模型与数据一致，例如，即使在低 LET 下也存在相当大的 DSB 聚类，平均每个聚类有 1.5 或更多反应性 DSB，但明显复杂的像差与明显简单的像差的比率是一致的。
PurposeFor high-LET radiations, and perhaps even for hard X-rays, DNA double-strand breaks (dsb) are clustered nonrandomly along chromosomes; disproportionately, many interdsb segments are less than a few Mbp (106 base pairs). The implications of such dsb clustering for chromosome aberrations are analysed.MethodsChromosome segments between different dsb within one dsb cluster are assumed too small to detect in the aberration assay. Enumeration or Monte-Carlo computer simulations are used to compute the relative frequencies of many observable aberration patterns: apparently simple or visibly complex. The theoretical predictions are compared with X-ray data for human fibroblasts, involving painted chromosomes 1, 2, 4, 5, 7 or 13.Results and conclusionsSurprisingly, cryptic dsb multiplicity does not affect the frequency ratios predicted for aberration patterns by a random breakage-and-rejoining model. The model is generally consistent with current data on many different types of aberrations, whether or not dsb usually occur in cryptic clusters. For a Revell-type exchange model, however, the predictions do depend on clustering configurations; they gradually approach the predictions of the breakage-and-rejoining model as average cluster multiplicity increases. The model is consistent with the data, for example with the ratio of visibly complex to apparently simple aberrations, only if there is considerable dsb clustering even at low-LET, with 1.5 or more reactive dsb per cluster on average.