Genetic susceptibility to radiation
Genetic susceptibility to radiation
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DOI：
10.1016/j.asr.2004.12.032
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Smilenov, L
中科院分区：
文献类型：
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作者：
Hall, EJ;Brenner, DJ;Smilenov, L
在空间辐射方面，重要的是要知道人口中是否包括遗传上易受辐射影响的亚群。一种可能性是ATM的单倍不足赋予放射敏感性，并且这种缺陷涉及1-3%的人群。使用基因敲除小鼠，我们选择研究透镜中的白内障发生和小鼠胚胎成纤维细胞中的致癌转化，以测定ATM缺陷的影响。辐射诱导的白内障出现较早的杂合子与野生型动物暴露于γ射线或1 GeV/核子铁离子。此外，还发现Aim杂合子的胚胎成纤维细胞与其正常同窝配对的胚胎成纤维细胞相比，其致癌转化的发生率增加。从这些数据中，我们认为，共济失调毛细血管扩张症杂合子确实可以代表一个社会显着的放射敏感性subpopulation. Knockout小鼠，现在可用于其他基因，包括BRCA 1和2，和Mrad 9。一个令人兴奋的可能性是为在同一信号转导途径中起作用的成对突变基因创造双杂合子，从而赋予更大的辐射敏感性。(c)Elsevier有限公司代表空间研委会出版。
In the context of space radiation, it is important to know whether the human population includes genetically predisposed radiosensitive subsets. One possibility is that haploinsufficiency for ATM confers radiosensitivity, and this defect involves 1-3% of the population. Using knock-out mice we chose to study cataractogenesis in the lens and oncogenic transformation in mouse embryo fibroblasts to assay for effects of ATM deficiency. Radiation induced cataracts appeared earlier in the heterozygous versus wild-type animals following exposure to either gamma rays or 1 GeV/nucleon iron ions. In addition, it was found that embryo fibroblasts of Aim heterozygotes showed an increased incidence of oncogenic transformation compared with their normal litter-matched counterparts. From these data we suggest that Ataxia Telangiectasia heterozygotes could indeed represent a societally significant radiosensitive subpopulation.Knock-out mice are now available for other genes including BRCA 1 and 2, and Mrad9. An exciting possibility is the creation of double heterozygotes for pairs of mutated genes that function in the same signal transduction pathway, and consequently confer even greater radiosensitivity. (c) 2004 Published by Elsevier Ltd on behalf of COSPAR.