Multiple origins of spontaneously arising micronuclei in HeLa cells: Direct evidence from long-term live cell imaging
Multiple origins of spontaneously arising micronuclei in HeLa cells: Direct evidence from long-term live cell imaging
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HeLa 细胞中自发产生的微核的多重起源：来自长期活细胞成像的直接证据
DOI：
10.1016/j.mrfmmm.2008.09.004
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发表时间：
2008-11-10
影响因子：
2.3
通讯作者：
Shi, Qinghua
中科院分区：
文献类型：
--
作者：
Rao, Xiaotang;Zhang, Yingyin;Shi, Qinghua
虽然微核（MNi）被广泛用于评价遗传毒性效应和染色体不稳定性，但由于传统方法的局限性，有关其起源的最基本问题尚未完全解决。最近，开发了长期活细胞成像，以实时和高通量的方式监测单细胞的动态。在本研究中，采用这种最先进的技术来检查未处理的HeLa细胞中自发微核（MN）的形成。我们证明，自发MNi来自不正确的排列染色体在中期（位移染色体，DC），落后染色体（LC）和断裂的染色体桥（CB）在后期有丝分裂阶段，但不是在S期的核芽。然而，大多数DC（91.29%）、LC（73.11%）和断裂CB（88.93%）的双极有丝分裂并未产生MNi。我们的数据还首次直接表明，MNi可以自发起源于（1）MNi已经存在于母细胞中;（2）在有丝分裂期间出现的核碎片与CB;（3）染色体被挤出到一个小细胞中，该小细胞后来与一个子细胞融合。MNi主要来源于LC（63.66%）、DC（10.97%）和断裂CB（9.25%）。总之，这些直接证据表明，在HeLa细胞中自发产生的MNi有多种来源，并且每种机制在不同程度上有助于整体MN的形成。(C)2008 Elsevier B. V.保留所有权利。
Although micronuclei (MNi) are extensively used to evaluate genotoxic effects and chromosome instability, the most basic issue regarding their origins has not been completely addressed due to limitations of traditional methods. Recently, long-term live cell imaging was developed to monitor the dynamics of single cell in a real-time and high-throughput manner. In the present study, this state-of-the-art technique was employed to examine spontaneous micronucleus (MN) formation in untreated HeLa cells. We demonstrate that spontaneous MNi are derived from incorrectly aligned chromosomes in metaphase (displaced chromosomes, DCs), lagging chromosomes (LCs) and broken chromosome bridges (CBs) in later mitotic stages, but not nuclear buds in S phase. However, most of bipolar mitoses with DCs (91.29%), LCs (73.11%) and broken CBs (88.93%) did not give rise to MNi. Our data also show directly, for the first time, that MNi could originate spontaneously from (1) MNi already presented in the mother cells; (2) nuclear fragments that appeared during mitosis with CB; and (3) chromosomes being extruded into a minicell which fused with one of the daughter cells later. Quantitatively, most of MNi originated from LCs (63.66%), DCs (10.97%) and broken CBs (9.25%). Taken together, these direct evidences show that there are multiple origins for spontaneously arising MNi in HeLa cells and each mechanism contributes to overall MN formation to different extents. (C) 2008 Elsevier B.V. All rights reserved.