The Contribution of Radiation-induced Large Deletion of the Genome to Chromosomal Instability
The Contribution of Radiation-induced Large Deletion of the Genome to Chromosomal Instability
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DOI：
10.1667/rr1464.1
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发表时间：
2009-02-01
影响因子：
3.4
通讯作者：
Watanabe, Masami
中科院分区：
文献类型：
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作者：
Toyokuni, Hideaki;Maruo, Atsushi;Watanabe, Masami
丰国，H.，Maruo，A.，铃木K. Watanabe，M.辐射诱导的基因组大缺失对染色体不稳定性的贡献。Radiat. 171，198-203（2009）.已知电离辐射诱导基因组不稳定性，其在存活细胞的后代的多代中传递。然而，辐射引起的基因组不稳定性的启动、持续和表现的机制仍不清楚。我们预计，大的辐射诱导的缺失，染色质的结构不稳定，这种不稳定是跨多代传递，并在基因组不稳定性的永久化中发挥作用。因此，在这项研究中，我们研究了缺失大小和SV 40永生化正常人成纤维细胞（GM 638）中迟发性染色体畸变频率之间的关系。用3戈伊的X射线照射GM 638细胞，并分析照射后衍生的克隆的染色体畸变。为了确定每个缺失的大小，我们从X射线照射的细胞群中分离出HPRT基因的突变体，并检查了位于X染色体q臂的HPRT基因座周围的基因。结果表明，具有大缺失（>0.5 Mb）的X染色体具有更高的概率表现出延迟染色体畸变，并且这些畸变在q臂中比在p臂中更频繁地被诱导。由于没有诱导X染色体不稳定性，观察克隆，缺乏这样的大缺失，目前的研究结果表明，染色体与大辐射诱导的缺失可能是基因组不稳定的。(C)2009年，辐射研究协会
Toyokuni, H., Maruo, A., Suzuki, K. and Watanabe, M. The Contribution of Radiation-Induced Large Deletion of the Genome to Chromosomal Instability. Radiat. Res. 171, 198-203 (2009).Ionizing radiation is known to induce genomic instability that is transmitted across many generations of the progeny of surviving cells. However, the mechanism underlying the initiation, perpetuation and manifestation of radiation-induced genomic instability remains unclear. We expect that large radiation-induced deletions destabilize the structure of chromatin and that this destabilization is transmitted across many generations and plays a role in the perpetuation of genomic instability. Therefore, in this study, we examined the relationship between deletion size and the frequency of delayed chromosomal aberrations in SV40-immortalized normal human fibroblast (GM638) cells. GM638 cells were irradiated with 3 Gy of X rays, and chromosomal aberrations were analyzed in clones derived after irradiation. To determine the size of each deletion, we isolated mutants of the HPRT gene from the X-irradiated cell population and examined the genes around the HPRT locus, which is located in the q-arm of chromosome X. The results indicated that X chromosomes with large (>0.5 Mb) deletions have a higher probability of exhibiting delayed chromosomal aberrations and that these aberrations were induced more frequently in q-arms than in p-arms. Because no induction of X-chromosomal instability was observed in clones that lacked such large deletions, the present findings suggest that chromosomes with large radiation-induced deletions can be genomically unstable. (C) 2009 by Radiation Research society