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超分辨率光学显微镜时代各种类型电离辐射照射下细胞 DNA 损伤与修复研究进展。

Advances in research of DNA damage and repair in cells exposed to various types of ionizing radiation in the era of super-resolution optical microscopy.

出版信息

Cas Lek Cesk. 2020 Winter;159(7-8):286-297.

Abstract

The present work introduces new findings about the influence of different radiation types on the cells, with the concern on the micro- and nanodosimetric aspects of chromatin damage. Emphasized is the relationship between the physical parameters of the incident radiation (g-rays, protons and high-LET heavy ions), character of chromatin damage, ability of cells to repair and survive DNA damage, and risk of genetic changes. While confirming a positive correlation between the LET of ionizing radiation, complexity of induced DNA double-strand breaks (DSB), and biological effectiveness (RBE) of radiation, at the same time, we show that our understanding of this relationship is only incomplete. Our discovery that various accelerated ions with similar LET can damage DNA in different ways and kill cells with unequal efficiency, could serve as an example. In addition, many aspects of DSB repair remain to be explained, for instance, how the cell activates the particular repair pathway at sites of individual DSBs, and how it depends on the radiation used and the chromatin architecture. The discussed results may be important, above all, for newly developing hadron therapy and in the context of manned interstellar flights planning. From the methodological point of view, we point to a tremendous progress in the field of optical microscopy and its research applications. In more detail, we introduce single-molecule localization microscopy (SMLM).

摘要

本工作介绍了不同辐射类型对细胞影响的新发现,重点关注染色质损伤的微观和纳观剂量学方面。强调了入射辐射(γ射线、质子和高传能线密度重离子)的物理参数、染色质损伤的特征、细胞修复和存活 DNA 损伤的能力以及遗传变化的风险之间的关系。虽然确认了电离辐射的 LET、诱导的 DNA 双链断裂(DSB)的复杂性和辐射的生物效应(RBE)之间存在正相关,但同时我们也表明,我们对这种关系的理解还不完全。我们的发现,即各种具有相似 LET 的加速离子可以以不同的方式损伤 DNA 并以不同的效率杀死细胞,可以作为一个例子。此外,DSB 修复的许多方面仍有待解释,例如,细胞如何在单个 DSB 部位激活特定的修复途径,以及它如何依赖于所使用的辐射和染色质结构。讨论的结果可能非常重要,特别是对于新发展的强子治疗和载人星际飞行计划的背景。从方法论的角度来看,我们指出了光学显微镜领域及其研究应用的巨大进展。更详细地说,我们介绍了单分子定位显微镜(SMLM)。

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