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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Biological effects in unirradiated human tissue induced by radiation damage up to 1 mm away
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Biological effects in unirradiated human tissue induced by radiation damage up to 1 mm away

机译：高达1毫米远的辐射损伤对未辐照人体组织的生物效应

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摘要

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.
机译：理解电离辐射的生物学效应的中心原则是，最初受影响的细胞被辐射直接破坏。相比之下，已经出现了有关“旁观者”反应的证据，该反应涉及对自身未被辐射直接穿过的附近细胞的损害。这些远程作用在机械上和评估低剂量暴露（仅直接击中一小部分细胞）的风险时都令人感兴趣。旁观者效应主要是通过使用不具有实际多细胞形态的体外单细胞系统观察到的。尚未在三维正常人体组织中报道任何研究。考虑到旁观者现象必须涉及细胞间相互作用，这种单细胞体外研究的相关性值得怀疑，因此，旁观者反应对人类健康的重要性仍不清楚。在这里，我们描述了三维正常人组织系统中的旁观者反应。终点是诱导微核细胞和凋亡细胞。使用带电粒子微束，可以照射组织中定义位置的细胞，但也可以确保距离几微米以外的任何细胞都不会受到任何辐射。与辐照细胞相距不超过1毫米的未辐照细胞显示出比背景显着增强的作用，微核的平均效应提高了1.7倍，凋亡的平均升高了2.8倍。人体组织中旁观者信号的范围之长令人惊讶，这表明在从流行病学上可及的剂量向下推算非命中的旁观者细胞占主导地位的极低剂量时，旁观者的反应可能对推断辐射风险估计很重要。

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