Chromosomal instability in the descendants of unirradiated surviving cells after α-particle irradiation
Chromosomal instability in the descendants of unirradiated surviving cells after α-particle irradiation
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DOI：
10.1073/pnas.95.10.5730
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发表时间：
1998-05-12
影响因子：
11.1
通讯作者：
Wright, EG
中科院分区：
文献类型：
--
作者：
Lorimore, SA;Kadhim, MA;Wright, EG
我们已经证明了用α粒子照射小鼠骨髓泥灰岩后，造血干细胞克隆后代的染色体不稳定性。然而，由于被α粒子照射的细胞由单个粒子穿越的泊松分布定义，因此存活群体中不可避免地存在未照射细胞的比例。计算出的辐照和未辐照细胞的预期比例表明，传递染色体不稳定性的克隆形成细胞的数量大于预期被击中并存活的数量。为了进一步研究这种差异，我们研究了在细胞和α粒子源之间插入网格的影响，使得存活的群体主要由未穿过的干细胞组成，与没有网格的相同照射条件的比较表明诱导了相同水平的不稳定性。这些数据证实，α粒子诱导染色体不稳定性，但不稳定性是在未照射的干细胞的后代中证明的，必须是由于照射和未照射的细胞之间的意外相互作用，这种非靶向效应具有重要意义的辐射作用的机制研究和辐射风险的评估。
We have demonstrated chromosomal instability in the clonal descendants of hemopoietic stem cells after irradiating murine bone marl ow with alpha-particles. However, because cells that are irradiated by alpha-particles are defined by a Poisson distribution of individual particle traversals, there is an inevitable proportion of unirradiated cells in the surviving population. The calculated expected proportions of irradiated and nonirradiated cells indicate that the number of clonogenic cells transmitting chromosomal instability is greater than the number expected to be hit and survive. To investigate further this discrepancy, we studied the effects of interposing a grid between the cells and the alpha-particle source so that the surviving population consists predominantly of untraversed stem cells, Comparison with the same irradiation conditions without the grid reveals that the same level of instability is induced. The data confirm that alpha-particles induct chromosomal instability but instability is demonstrated in the progeny of nonirradiated stem cells and must be due to unexpected interactions between irradiated and nonirradiated cells, This untargeted effect has important implications for mechanistic studies of radiation action and for assessment of radiation risk.