Spectrum of X-ray-induced mutations in the human hprt gene.
Spectrum of X-ray-induced mutations in the human hprt gene.
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X 射线诱导的人类 hprt 基因突变谱。
DOI：
10.1093/carcin/15.3.495
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发表时间：
1994
期刊：
影响因子：
4.7
通讯作者：
Grosovsky,AJ
中科院分区：
文献类型：
--
作者：
Nelson,SL;Giver,CR;Grosovsky,AJ
我们对源自人 B 类淋巴母细胞系 TK6 的 116 个 X 射线诱导突变体和 78 个自发 HPRT-突变体的突变分子谱进行了表征。多重 PCR 分析表明，两个光谱中大缺失的总体表现没有显着差异。然而，对于特定的缺失类型观察到高度显着的差异。总基因缺失占 X 射线诱导的 41/78 (0.53)，但仅 7/43 (0.16) 自发缺失 (P < 0.0001)。相比之下，自发性 (17/43, 0.40) 的 5' 末端缺失明显比 X 射线诱导的 (13/78, 0.17) 大缺失更常见 (P = 0.0079)。 X射线照射诱导的点突变类型非常多样，包括所有类别的转换和颠换、串联碱基取代、移码、小缺失和缺失/插入复合突变。与自发数据相比，辐射诱导的点突变表现出转变数量减少和小缺失的增加。小缺失均匀地被直接序列重复包围。点突变的分布特征是外显子 8 5' 部分内的簇。13 个 HPRT-点突变表现出异常尖峰。其中四个可归因于外显子 4 和 8 的编码序列改变。这些结果表明，有可能识别与人类细胞 X 射线暴露相关的标志性突变。
We have characterized the molecular spectrum of mutations in 116 X-ray-induced and 78 spontaneous, HPRT−mutants derived from the human B lymphoblastoid cell line TK6. Multiplex PCR analysis demonstrated that the overall representation of large deletions was not significantly different in the two spectra. However, highly significant differences were observed for specific deletion types. Total gene deletions represented 41/78 (0.53) X-ray-induced, but only 7/43 (0.16) spontaneous deletions (P < 0.0001). In contrast, 5′ terminal deletions were significantly more common among spontaneous (17/43, 0.40) than X-ray-induced (13/78, 0.17) large deletions {P = 0.0079). The types of point mutations induced by X-ray exposure were very diverse including all classes of transitions and transversions, tandem base substitutions, frameshifts, small deletions and a deletion/insertion compound mutation. Compared to spontaneous data, radiation-induced point mutations exhibited a reduced number of transitions and an increased representation of small deletions. Small deletions were uniformly surrounded by direct sequence repeats. The distribution of point mutations was characterized by a cluster within the 5′ portion of exon 8. Thirteen HPRT−point mutations exhibited aberrant spiking. Four of these were attributable to coding sequence alterations in exons 4 and 8. These results suggest that it may be possible to identify hallmark mutations associated with X-ray exposure of human cells.