Mutagenic effects of a single and an exact number of alpha particles in mammalian cells
Mutagenic effects of a single and an exact number of alpha particles in mammalian cells
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DOI：
10.1073/pnas.94.8.3765
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发表时间：
1997-04-15
影响因子：
11.1
通讯作者：
RandersPehrson, G
中科院分区：
文献类型：
--
作者：
Hei, TK;Wu, LJ;RandersPehrson, G
使用地下矿工肺癌数据进行环境氡暴露风险估计的主要不确定性之一是从高剂量暴露到低剂量暴露的外推，其中多次穿越极为罕见。单个α粒子的生物效应目前尚不清楚。利用哥伦比亚大学放射学研究加速器设施最近可用的微束源，我们检查了由单个或精确数量的α粒子在人-仓鼠杂交（A（L））细胞中诱导的S1（-）突变体的频率和分子谱。用无毒浓度的Hoechst染料对指数生长的细胞进行短暂染色以进行图像分析，并通过计算机监测单个细胞的位置。每个细胞的细胞核被照射与国内氡暴露的能谱一致的线性能量转移90千电子伏/微米的1，2，4，或8 α粒子。虽然单粒子穿越对A（L）细胞只有轻微的细胞毒性（存活分数约为0.82），但它具有高度的致突变性，每10（5）个存活细胞平均诱导110个突变体。此外，毒性和突变体诱导均呈剂量依赖性。突变体DNA的多重PCR分析表明，艾德多位点缺失突变体的比例随着粒子穿越次数的增加而增加。这些数据提供了直接的证据，表明单个α粒子穿过细胞核将有很高的可能性导致突变，并强调了低剂量辐射防护的必要性。
One of the main uncertainties in risk estimation for environmental radon exposure using lung cancer data from underground miners is the extrapolation from high- to low-dose exposure where multiple traversal is extremely rare. The biological effects of a single alpha particle are currently unknown. Using the recently available microbeam source at the Radiological Research Accelerator Facility at Columbia University, we examined the frequencies and molecular spectrum of S1(-) mutants induced in human-hamster hybrid (A(L)) cells by either a single or an exact number of alpha particles. Exponentially growing cells were stained briefly with a nontoxic concentration of Hoechst dye for image analysis, and the location of individual cells was computer-monitored. The nucleus of each cell was irradiated with either 1, 2, 4, or 8 alpha particles at a linear energy transfer of 90 keV/mu m consistent with the energy spectrum of domestic radon exposure. Although single-particle traversal was only slightly cytotoxic to A(L) cells (survival fraction approximate to 0.82), it was highly mutagenic, and the induced mutant fraction averaged 110 mutants per 10(5) survivors. In addition, both toxicity and mutant induction were dose-dependent. Multiplex PCR analysis of mutant DNA show ed that the proportion of mutants with multilocus deletions increased with the number of particle traversals. These data provide direct evidence that a single alpha particle traversing a nucleus will have a high probability of resulting in a mutation and highlight the need for radiation protection at low doses.