Biological effects in unirradiated human tissue induced by radiation damage up to 1 mm away
Biological effects in unirradiated human tissue induced by radiation damage up to 1 mm away
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DOI：
10.1073/pnas.0505020102
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发表时间：
2005-10-04
影响因子：
11.1
通讯作者：
Brenner, DJ
中科院分区：
文献类型：
--
作者：
Belyakov, OV;Mitchell, SA;Brenner, DJ
理解电离辐射生物效应的一个核心原则是，最初受影响的细胞直接受到辐射的损害。相比之下，已经出现了关于“旁观者”反应的证据，这些反应涉及对附近细胞的损伤，而这些细胞本身并没有被辐射直接穿过。这些长期效应在机制上和评估低剂量照射的风险方面都很有意义，因为只有一小部分细胞直接受到影响。旁观者效应主要是通过使用不具有现实多细胞形态的单细胞体外系统观察到的;尚未报道在三维正常人体组织中的研究。鉴于旁观者现象必须涉及细胞与细胞的相互作用，这种单细胞体外研究的相关性是值得怀疑的，因此旁观者反应对人类健康的意义仍然不清楚。在这里，我们描述了旁观者的反应，在一个三维的，正常的人体组织系统。终点为微核和凋亡细胞的诱导。使用带电粒子微束，允许照射组织中指定位置的细胞，但保证距离超过几微米的细胞不会受到任何辐射。未照射的细胞距离照射的细胞1毫米显示出显着增强的效果超过背景，与平均增加的影响为1.7倍的微核和2.8倍的凋亡。人体组织中旁观者信号的范围之长令人惊讶，这表明旁观者反应在从流行病学上可获得的剂量外推辐射风险估计到非命中旁观者细胞将占主导地位的非常低的剂量方面可能是重要的。
A central tenet in understanding the biological effects of ionizing radiation has been that the initially affected cells were directly damaged by the radiation. By contrast, evidence has emerged concerning "bystander" responses involving damage to nearby cells that were not themselves directly traversed by the radiation. These long-range effects are of interest both mechanistically and for assessing risks from low-dose exposures, where only a small proportion of cells are directly hit. Bystander effects have been observed largely by using single-cell in vitro systems that do not have realistic multicellular morphology; no studies have as yet been reported in three-dimensional, normal human tissue. Given that the bystander phenomenon must involve cell-to-cell interactions, the relevance of such single-cell in vitro studies is questionable, and thus the significance of bystander responses for human health has remained unclear. Here, we describe bystander responses in a three-dimensional, normal human-tissue system. Endpoints were induction of micronucleated and apoptotic cells. A charged-particle microbeam was used, allowing irradiation of cells in defined locations in the tissue yet guaranteeing that no cells located more than a few micrometers away receive any radiation exposure. Unirradiated cells up to 1 mm distant from irradiated cells showed a significant enhancement in effect over background, with an average increase in effect of 1.7-fold for micronuclei and 2.8-fold for apoptosis. The surprisingly long range of bystander signals in human tissue suggests that bystander responses may be important in extrapolating radiation risk estimates from epidemiologically accessible doses down to very low doses where nonhit bystander cells will predominate.