Propagation distance of the alpha-particle-induced bystander effect: the role of nuclear traversal and gap junction communication.

Propagation distance of the alpha-particle-induced bystander effect: the role of nuclear traversal and gap junction communication.
复制标题

α粒子诱导的旁观者效应的传播距离:核遍历和间隙连接通信的作用。

DOI:
10.1667/rr1658.1
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发表时间:
2009-05
期刊:
影响因子:
3.4
通讯作者:
Azzam EI
Azzam EI
中科院分区:
医学3区
文献类型:
--
作者:
Gaillard S;Pusset D;de Toledo SM;Fromm M;Azzam EI

文献摘要

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当细胞群暴露于低剂量α粒子辐射时,很大一部分细胞将不会被辐射径迹穿过。然而,群体中受辐射的细胞和旁观者细胞都发生了应激效应。描述这些效应并研究其潜在机制,对于了解与接触α粒子相关的人类健康风险至关重要。为此,将融合的正常人成纤维细胞培养物生长在接枝到固态核径迹探测器的聚对苯二甲酸乙二醇酯箔上,并在非扰动条件下暴露于来自宽束辐照器的低通量α粒子。以微米精度定位辐射和受影响的旁观者细胞。应激反应蛋白p21 Waf1(也称为CDKN1A)在距离辐射细胞100 µm半径内的旁观者细胞中诱导。在核内α粒子撞击点周围,平均传播距离范围为20至40 µm,这相当于一组30个细胞。核穿越、诱导的DNA损伤和间隙连接通讯是这种应激效应传播的关键因素。本文描述的策略可能是理想的,以研究受辐射影响的靶点的大小和不同细胞器对高能粒子诱导的旁观者效应的相对贡献,这与辐射防护和癌症放疗有关。
When cell populations are exposed to low-dose α-particle radiation, a significant fraction of the cells will not be traversed by a radiation track. However, stressful effects occur in both irradiated and bystander cells in the population. Characterizing these effects, and investigating their underlying mechanism(s), is critical to understanding human health risks associated with exposure to α particles. To this end, confluent normal human fibroblast cultures were grown on polyethylene terephthalate foil grafted to an ultrathin solid-state nuclear track detector and exposed under non-perturbing conditions to low-fluence α particles from a broadbeam irradiator. Irradiated and affected bystander cells were localized with micrometer precision. The stress-responsive protein p21Waf1 (also known as CDKN1A) was induced in bystander cells within a 100-µm radius from an irradiated cell. The mean propagation distance ranged from 20 to 40 µm around the intranuclear α-particle impact point, which corresponds to a set of ∼30 cells. Nuclear traversal, induced DNA damage, and gap junction communication were critical contributors to propagation of this stressful effect The strategy described here may be ideal to investigate the size of radiation-affected target and the relative contribution of different cellular organelles to bystander effects induced by energetic particles, which is relevant to radioprotection and cancer radiotherapy.