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辐射诱导的染色质断裂的重新连接和错误重新连接。I. 对人类淋巴细胞的实验。

Rejoining and misrejoining of radiation-induced chromatin breaks. I. experiments with human lymphocytes.

作者信息

Durante M, George K, Wu H, Yang T C

机构信息

NASA Lyndon B. Johnson Space Center, Radiation Biophysics Laboratory, Houston, Texas 77058, USA.

出版信息

Radiat Res. 1996 Mar;145(3):274-80.

PMID:8927694
Abstract

Fluorescence in situ hybridization with a composite probe for human chromosome 4 and a probe that stained all centromeres was used to study gamma-ray induced breakage, rejoining and misrejoining in prematurely condensed chromosomes in human lymphocytes. Dose-response curves for the induction of all types of aberrations in prematurely condensed human chromosomes 4 were determined immediately after irradiation and after 8 h postirradiation incubation. In addition, aberrations were measured after various incubation times from 0 to 18 h after a dose of 7 Gy. Unrejoined chromosome breaks were the most frequent type of aberration observed immediately after irradiation. Approximately 15% of total aberrations observed were chromosome exchanges. After 8 h postirradiation incubation, the frequency of breaks in prematurely condensed chromosomes declined to about 20% of the initial value, and chromosomal exchanges became the most frequent aberration. Results of metaphase analysis were similar to those for prematurely condensed chromosomes after 8 h incubation with the exception that a significantly lower frequency of fragments was observed. Symmetrical and asymmetrical interchanges were found at similar frequencies at all doses. No complex exchanges were observed in lymphocyte chromosomes immediately after exposure. They accounted for about 1% of total exchanges in metaphase chromosomes at doses <3 Gy and about 14% at 7 Gy. Incomplete exchanges amounted to approximately 15% of total exchanges at all doses. The kinetics of break rejoining was exponential, and the frequency of exchanges increased with kinetics similar to that observed for the rejoining of the breaks. This increase in the total exchanges as a function of the time between irradiation and fusion was due to a rapid increase in reciprocal interchanges, and a slower increase in complex exchanges; the frequency of incomplete exchanges increased initially, then decreased with prolonged incubation to the level observed in metaphase. It is concluded that the formation of each kind of chromosome aberrations follows different kinetics.

摘要

采用针对人类4号染色体的复合探针和一种能使所有着丝粒染色的探针进行荧光原位杂交,以研究γ射线诱导的人类淋巴细胞中早凝染色体的断裂、重接和错接情况。在照射后即刻以及照射后8小时孵育后,测定了早凝人类4号染色体中各类畸变诱导的剂量反应曲线。此外,在给予7 Gy剂量后,于0至18小时的不同孵育时间后测量了畸变情况。照射后即刻观察到的最常见畸变类型是未重接的染色体断裂。观察到的总畸变中约15%为染色体交换。照射后8小时孵育后,早凝染色体中的断裂频率降至初始值的约20%,染色体交换成为最常见的畸变。中期分析结果与孵育8小时后的早凝染色体结果相似,只是观察到的片段频率明显更低。在所有剂量下,对称和不对称互换的频率相似。暴露后即刻在淋巴细胞染色体中未观察到复杂交换。在剂量<3 Gy时,它们占中期染色体总交换的约1%,在7 Gy时约占14%。在所有剂量下,不完全交换约占总交换的15%。断裂重接的动力学呈指数形式,交换频率的增加与观察到的断裂重接动力学相似。这种总交换随照射与融合之间时间的增加是由于相互互换的快速增加以及复杂交换的缓慢增加;不完全交换的频率最初增加,然后随着孵育时间延长而降低至中期观察到的水平。得出的结论是,每种染色体畸变的形成遵循不同的动力学。

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Comparison of the repair of potentially lethal damage after low- and high-LET radiation exposure, assessed from the kinetics and fidelity of chromosome rejoining in normal human fibroblasts.
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