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人成纤维细胞中由高线性能量转移辐射产生的双链断裂处正确与错误DNA末端的连接。

Joining of correct and incorrect DNA ends at double-strand breaks produced by high-linear energy transfer radiation in human fibroblasts.

作者信息

Löbrich M, Cooper P K, Rydberg B

机构信息

Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley 94720, USA.

出版信息

Radiat Res. 1998 Dec;150(6):619-26.

PMID:9840181
Abstract

DNA double-strand breaks (DSBs) were measured within a 3.2-Mbp NotI fragment on chromosome 21 of cells of a normal human fibroblast cell line. Correct rejoining of DSBs was followed by measuring reconstitution of the original-size NotI fragment, and this was compared to total rejoining as measured by a conventional pulsed-field gel electrophoresis technique (FAR assay). After 80 Gy of particle irradiations with LETs in the range of 7-150 keV/microm, it was found that the repair kinetics was generally slower after irradiation with high-LET particles compared to X irradiation and that a larger proportion of the breaks remained unrepaired after 24 h. On the other hand, the misrejoining frequency as measured by the difference between correct and total rejoining after 24 h did not change with LET, but was approximately the same for all radiations at this dose, equal to 25-30% of the initial breaks. This result is discussed in relation to formation of chromosomal aberrations, deletion mutations and other biological end points.

摘要

在一个正常人成纤维细胞系的细胞中,对21号染色体上一个3.2兆碱基对的NotI片段内的DNA双链断裂(DSB)进行了测量。通过测量原始大小的NotI片段的重建来跟踪DSB的正确重新连接,并将其与通过传统脉冲场凝胶电泳技术(FAR分析)测量的总重新连接进行比较。在用7-150 keV/微米范围内的线性能量传递(LET)进行80 Gy的粒子照射后,发现与X射线照射相比,高LET粒子照射后的修复动力学通常较慢,并且在24小时后仍有较大比例的断裂未修复。另一方面,通过24小时后正确重新连接和总重新连接之间的差异测量的错误重新连接频率不会随LET变化,而是在该剂量下所有辐射的情况大致相同,等于初始断裂的25-30%。结合染色体畸变、缺失突变和其他生物学终点的形成对该结果进行了讨论。

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