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辐射产生的染色体畸变比率作为间期大规模DNA几何结构的指标。

Ratios of radiation-produced chromosome aberrations as indicators of large-scale DNA geometry during interphase.

作者信息

Sachs R K, Awa A, Kodama Y, Nakano M, Ohtaki K, Lucas J N

机构信息

Department of Physics, University of California, Berkeley 94720.

出版信息

Radiat Res. 1993 Mar;133(3):345-50.

PMID:8451385
Abstract

Chromosome aberrations produced by ionizing radiation are assumed to develop from DNA double-strand breaks (DSBs) which interact pairwise. Stable chromosome aberrations that exemplify inter- and intra-chromosomal exchanges are, respectively, translocations and pericentric inversions. By comparing the number of these for each chromosome one can infer results on the randomness of DSB induction or exchange formation and on large-scale chromosome geometry. We analyze frequencies of translocations and pericentric inversions in lymphocytes from 38 A-bomb survivors, using G-banding. A total of 636 translocations and 102 pericentric inversions were found. The 636/102 ratio of translocations to pericentric inversions is approximately 14 times smaller than predicted by a random model, in general agreement with earlier results and results on the ratio of dicentrics to centric rings for in vitro irradiation. Presumably the excess of intra-chromosomal exchanges is due to a spatial proximity effect, implying a localization of chromosomes within the cell nucleus during and shortly after irradiation. The distribution of the pericentric inversions among different chromosomes indicates this proximity effect is roughly the same for all chromosomes, regardless of DNA content; i.e., the ratio of pericentric inversions for two different chromosomes approximately equals the ratio given by a model which takes into account chromosome lengths and centromere locations but otherwise assumes randomness. Possible exceptions are chromosomes 7 and 12, which show some excess of pericentric inversions. The percentage of translocations involving each chromosome corresponds roughly to the percentage expected assuming randomness, except that for chromosome 1 there is a significant excess.

摘要

电离辐射产生的染色体畸变被认为是由两两相互作用的DNA双链断裂(DSB)发展而来的。体现染色体间和染色体内交换的稳定染色体畸变分别是易位和臂间倒位。通过比较每条染色体上这些畸变的数量,可以推断出关于DSB诱导或交换形成的随机性以及大规模染色体几何结构的结果。我们使用G显带技术分析了38名原子弹爆炸幸存者淋巴细胞中的易位和臂间倒位频率。总共发现了636个易位和102个臂间倒位。易位与臂间倒位的636/102比例大约比随机模型预测的小14倍,这与早期结果以及体外照射时双着丝粒与中心环比例的结果总体一致。推测染色体内交换的过量是由于空间邻近效应,这意味着在照射期间和照射后不久染色体在细胞核内的定位。臂间倒位在不同染色体间的分布表明,所有染色体的这种邻近效应大致相同,与DNA含量无关;即,两条不同染色体的臂间倒位比例大约等于一个考虑了染色体长度和着丝粒位置但其他方面假设为随机的模型给出的比例。可能的例外是7号和12号染色体,它们显示出臂间倒位有一些过量。涉及每条染色体的易位百分比大致对应于假设为随机时预期的百分比,只是1号染色体有显著过量。

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