Heavy-ion-induced mutations in the gpt delta transgenic mouse:: Comparison of mutation spectra induced by heavy-ion, X-ray, and γ-ray radiation
Heavy-ion-induced mutations in the gpt delta transgenic mouse:: Comparison of mutation spectra induced by heavy-ion, X-ray, and γ-ray radiation
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DOI：
10.1002/em.10108
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发表时间：
2002-01-01
影响因子：
2.8
通讯作者：
Nohmi, T
中科院分区：
文献类型：
--
作者：
Masumura, K;Kuniya, K;Nohmi, T
重离子辐射是吸收的宇宙辐射的主要组成部分，因此被认为是长期载人航天飞行期间的重大危险。为了评估重粒子辐射对gpt delta转基因小鼠的遗传损伤，我们将gpt delta转基因小鼠暴露于碳粒子辐射下，并将其诱导突变与参考辐射（即x射线和伽马射线）诱导的突变进行比较。在转基因小鼠模型中，缺失和点突变分别被鉴定为Spi（-）和gpt突变。10 Gy全身照射2 d后，测定Spi（-）和gpt的突变频率（MFs）。碳粒子辐照显著增加肝脏、脾脏和肾脏的Spi(-) MF，但在睾丸中没有，提示重离子辐照可诱导器官特异性突变。在肝脏中，碳颗粒诱导Spi（-）突变的效力最高（增加3.3倍），其次是x射线（增加2.1倍）和伽马射线（增加1.3倍），而诱导gpt突变的效力最高的是伽马射线（增加3.3倍），其次是x射线（增加2.1倍）和碳颗粒（增加1.6倍）。DNA序列分析显示，碳粒子引起的缺失主要是超过1000个碱基对的大小，而伽马射线引起的缺失小于100个碱基对和碱基取代。x射线引起不同大小的缺失和碱基取代。这些结果表明，重离子束辐照在通过DNA双链断裂诱导DNA缺失方面是有效的，但在产生自由基引起的DNA氧化损伤方面不如x射线和伽马射线辐照有效。(C) 2002 Wiley-Liss, Inc。
Heavy-ion radiation accounts for the major component of absorbed cosmic radiation and is thus regarded as a significant risk during long-term manned space missions. To evaluate the genetic damage induced by heavy particle radiation, gpt delta transgenic mice were exposed to carbon particle irradiation and the induced mutations were compared with those induced by reference radiations, i.e., X-rays and gamma-rays. In the transgenic mouse model, deletions and point mutations were individually identified as Spi(-) and gpt mutations, respectively. Two days after 10 Gy of whole-body irradiation, the mutant frequencies (MFs) of Spi(-) and gpt were determined. Carbon particle irradiation significantly increased Spi(-) MF in the liver, spleen, and kidney but not in the testis, suggesting an organ-specific induction of mutations by heavy-ion irradiation. In the liver, the potency of inducing Spi(-) mutation was highest for carbon particles (3.3-fold increase) followed by X-rays (2.1-fold increase) and gamma-rays (1.3-fold increase), while the potency of inducing gpt mutations was highest for gamma-rays (3.3-fold increase) followed by X-rays (2.1-fold increase) and carbon particles (1.6-fold increase). DNA sequence analysis revealed that carbon particles induced deletions that were mainly more than 1,000 base pairs in size, whereas gamma-rays induced deletions of less than 100 base pairs and base substitutions. X-rays induced various-sized deletions and base substitutions. These results suggest that heavy-ion beam irradiation is effective at inducing deletions via DNA double-strand breaks but less effective than X-ray and gamma-ray irradiation at producing oxidative DNA damage by free radicals. (C) 2002 Wiley-Liss, Inc.