Cellular and molecular effects for mutation induction in normal human cells irradiated with accelerated neon ions

Cellular and molecular effects for mutation induction in normal human cells irradiated with accelerated neon ions
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DOI:
10.1016/j.mrfmmm.2005.08.007
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发表时间:
2006-02-22
影响因子:
2.3
通讯作者:
Watanabe, M
Watanabe, M
中科院分区:
医学4区
文献类型:
--
作者:
Suzuki, M;Tsuruoka, C;Watanabe, M

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我们研究了线性能量转移(LET)依赖于次黄嘌呤-鸟嘌呤磷酸核糖转移酶(HPRT)基因座在正常人成纤维细胞样细胞的突变诱导与加速γ-离子束照射。细胞照射在各种LET范围从63至335千电子伏/μ m的电子束。氖离子束由日本物理化学研究所的Riken环形回旋加速器加速。检测HPRT基因座处的突变诱导以测量6-硫代鸟嘌呤抗性克隆。采用多重聚合酶链反应(PCR)分析突变体外显子缺失模式的突变谱。与对Cs-137 γ射线的反应相比,剂量-反应曲线在高达0.5戈伊时急剧增加,在0.5和1.0戈伊之间趋于平稳或下降。突变频率增加到105千电子伏/亩米,然后有一个下降的趋势,随着LET值的增加。外显子缺失模式为非特异性。约75-100%的突变体产生的LETs范围从63至335 keV/μ m显示全部或部分缺失的外显子,而在γ射线诱导的突变体中,30%显示没有缺失,30%部分缺失和40%完全缺失。这些结果表明,LET值对离子诱发突变的剂量-反应曲线有一定的依赖性,而对DNA的缺失模式无明显的依赖性。(c)2005 Elsevier B. V.保留所有权利。
We investigated the linear energy transfer (LET) dependence of mutation induction on the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus in normal human fibroblast-like cells irradiated with accelerated neon-ion beams. The cells were irradiated with neon-ion beams at various LETs ranging from 63 to 335 keV/mu m. Neon-ion beams were accelerated by the Riken Ring Cyclotron at the Institute of Physical and Chemical Research in Japan. Mutation induction at the HPRT locus was detected to measure 6-thioguanine-resistant clones. The mutation spectrum of the deletion pattern of exons of mutants was analyzed using the multiplex polymerase chain reaction (PCR). The dose-response curves increased steeply up to 0.5 Gy and leveled off or decreased between 0.5 and 1.0 Gy, compared to the response to Cs-137 gamma-rays. The mutation frequency increased up to 105 keV/mu m and then there was a downward trend with increasing LET values. The deletion pattern of exons was non-specific. About 75-100% of the mutants produced using LETs ranging from 63 to 335 keV/mu m showed all or partial deletions of exons, while among gamma-ray-induced mutants 30% showed no deletions, 30% partial deletions and 40% complete deletions. These results suggested that the dose-response curves of neon-ion-induced mutations were dependent upon LET values, but the deletion pattern of DNA was not. (c) 2005 Elsevier B.V. All rights reserved.