Modelling the formation of polycentric chromosome aberrations.

Modelling the formation of polycentric chromosome aberrations.
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模拟多中心染色体畸变的形成。

DOI:
10.1080/09553009214552331
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发表时间:
1992
影响因子:
2.6
通讯作者:
Morgan,WF
Morgan,WF
中科院分区:
医学3区
文献类型:
--
作者:
Sachs,RK;Yates,BL;Tarver,J;Morgan,WF

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电离辐射或限制性内切酶产生的交换型染色体畸变被认为是DNA双链断裂(dsb)的成对相互作用造成的。除了双着丝粒,这种畸变还可以包括更高阶的多着丝粒(三着丝粒、四着丝粒等)。我们已经开发了计算机程序,可以计算给定平均成对相互作用数的各种多中心体的概率。使用了两种模型。模型I采用了恢复,完全交换(非法重组事件)和不完全交换之间的动力学竞争。模型II允许即使没有重组也不能恢复的断裂。将该模型应用于G1期中国仓鼠卵巢细胞经限制性内切酶PvuII电穿孔后产生的畸变的实验观察。我们发现,实验和理论上,有一个最大的多中心的数量和多样性,每个细胞:超过一定的PvuII浓度没有额外的或高阶多中心产生。计算机生成的关系,这是非常相似的两个模型和可调参数的所有值,被发现之间的双中心每细胞和高阶多中心每细胞。实验观察结果与理论上的一致性曲线吻合得很好,理论上的一致性曲线是三着丝粒/细胞和双着丝粒/细胞。对于给定数量的双着丝粒细胞,观察到的每个细胞的较高多着丝粒细胞的数量略大于共识理论预测。观察到的每个细胞的中心环的数量明显大于共识的理论值,大概是由于染色体内定位(“邻近效应”)。计算机模型还提供了可调参数的估计值;例如,在模型I中,发现不完全交换的比例约为35%。
Exchange-type chromosome aberrations produced by ionizing radiation or restriction enzymes are believed to result from pairwise interaction of DNA double-strand breaks (dsb). In addition to dicentrics, such aberrations may include higher-order polycentrics (tricentrics, tetracentrics, etc.). We have developed computer programs that calculate the probability of the various polycentrics for a given average number of pairwise interactions. Two models are used. Model I incorporates kinetic competition between restitution, complete exchanges (illegitimate recombination events), and incomplete exchanges. Model II allows unrestituted breaks even if there is no recombination. The models were applied to experimental observations of aberrations produced in G1Chinese hamster ovary cells after electroporation with the restriction enzymePvuII, which produces blunt-end dsb. We found, experimentally and theoretically, that there was a maximum in the number and multiplicity of polycentrics per cell: beyond a certainPvuII concentration no additional or higher-order polycentrics were produced. Computer-generated relationships, which were remarkably similar for both models and for all values of the adjustable parameters, were found between dicentrics per cell and higher-order polycentrics per cell. Excellent agreement was found between the experimental observations and the consensus theoretical curve relating tricentrics per cell to dicentrics per cell. The observed number of higher polycentrics per cell for a given number of dicentrics per cell was somewhat larger than the consensus theoretical prediction. The observed number of centric rings per cell was markedly larger than the consensus theoretical value, presumably owing to intrachromosomal localization (‘proximity effects’). The computer models also provided estimates for the adjustable parameters; for example, in model I the fraction of incomplete exchanges was found to be about 35%.
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发表时间: 1991
期刊: Radiation research
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