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[暴露于适应性剂量X射线对正常及DNA双链断裂修复缺陷的人类淋巴细胞诱导的结构和功能变化]

[Structural and functional changing induced by exposure to adaptive doses of X-rays in the human lymphocytes both normal and defective by reparation of DNA double strands breaks].

作者信息

Spitkovskiĭ D M, Veĭko N N, Ermakov A V, Kuz'mina I V, Makarenkov A S, Salimov A G, Terekhov S M, Karpukhin A V

机构信息

State Research Center for Medical Genetics, Russian Academy of Medical Sciences, Moscow, 115478 Russia.

出版信息

Radiats Biol Radioecol. 2003 Mar-Apr;43(2):136-43.

Abstract

In the present work it is shown that the phenomenon of interphase chromosome centromeric region displacement, earlier revealed by the authors, is not realized in G0-lymphocytes with heterozygous BRCA1/2 gene mutations. The role of these genes in DNA double strand break (DSB) reparation is known. It is concluded that chromosome locus displacement is necessary for DSB repair, at least in the process of homologous recombination. In accordance with our data, some feature (pericentromeric cluster disintegration and displacement, the nucleus size increasing) characteristic for S- and G0-lymphocytes are observed in normal G0-lymphocytes treated with 3 and 10 cGy. However, the size of nucleus in G0-lymphocytes is restored through 6 hours after irradiation in opposite to the process in dividing cells. It was proposed that some typical for resting cell functions of G0-lymphocytes after inducing by adaptive doze of radiation are stopped as similarly as after stimulation of cells. Interestingly, that the process of the induced chromosome loci displacement is correlated with the decreasing of DNA reparation possibilities under UV-irradiation. The induced apoptosis level also decreases when chromosome loci are displaced. The possible mechanisms of the revealed phenomenon are discussed. This research supported by RFBR grant (No. 01-04-49180).

摘要

在本研究中表明,作者先前发现的间期染色体着丝粒区域位移现象,在具有杂合BRCA1/2基因突变的G0淋巴细胞中并未出现。已知这些基因在DNA双链断裂(DSB)修复中所起的作用。得出的结论是,至少在同源重组过程中,染色体位点位移对于DSB修复是必要的。根据我们的数据,在用3和10 cGy照射的正常G0淋巴细胞中,观察到了一些S期和G0期淋巴细胞特有的特征(着丝粒周围簇解体和位移、细胞核大小增加)。然而,与分裂细胞的过程相反,G0淋巴细胞的细胞核大小在照射后6小时恢复。有人提出,G0淋巴细胞在适应性剂量辐射诱导后,一些静止细胞典型的功能会像细胞受到刺激后一样停止。有趣的是,诱导的染色体位点位移过程与紫外线照射下DNA修复可能性的降低相关。当染色体位点发生位移时,诱导的凋亡水平也会降低。讨论了所揭示现象的可能机制。本研究得到俄罗斯基础研究基金会资助(项目编号:01 - 04 - 49180)。

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