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近年来,由于放疗技术和核能的发展,人们越来越多地关注电离辐射对生物体造成的各种影响。长久以来,人们一直认为电离辐射损伤的主要靶点是细胞核中的DNA,然而近年来有报道,电离辐射有直接效应和间接效应,间接效应中的活性氧损伤学说认为电离辐射具有靶标不确定性,只评价细胞核中的DNA损伤已经显得不够全面。电离辐射后基因表达的异常以及染色体组的不稳定性等辐射间接造成的遗传效应[1],使辐射生物学面临新的挑战。
有报道指出电离辐射除了导致细胞损伤效应,还会导致细胞器受到损伤[2]。线粒体是受到损伤的重要细胞器,因为在细胞质中线粒体占据整个细胞容积的30%之多,其中含有的DNA和相关的酶与细胞ATP合成、有氧呼吸等生命活动息息相关。更值得注意的是,线粒体是人体唯一有DNA存在的细胞器,这使研究者对电离辐射导致的线粒体DNA的各种损伤(如双链的断裂、碱基的错配以及片段的丢失)引起重视。虽然这些损伤在细胞核也会发生,但是由于线粒体DNA缺乏组蛋白保护,其损伤比细胞核DNA更严重,因此线粒体是除细胞核以外电离辐射损伤的重要靶点。
电离辐射对线粒体的功能产生影响,使线粒体有氧呼吸链遭到破坏,线粒体处于氧化应激状态,最终激活线粒体凋亡通路使细胞凋亡[3]。同时,辐射会导致编码有氧呼吸链蛋白的DNA发生损伤,影响有氧呼吸中ATP的产生,对细胞的存活构成威胁[4]。可以看出,线粒体是辐射损伤并诱导凋亡的首要靶标。即便线粒体在电离辐射损伤中有如此重要的地位,但仍不能完全取代现有的细胞辐射损伤评价模型的评价指标,现有的评价指标依旧集中在细胞核及其遗传物质上。
由于对电离辐射所致线粒体损伤效应的研究远远少于对细胞核的研究,因此,本文概括了一些受到电离辐射后线粒体的应答,并把线粒体对细胞整体应激反应的重要性做了一些归纳。
电离辐射对线粒体损伤的研究进展
Damages of ionizing radiation on mitochondria
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摘要: 细胞核中的DNA被认为是电离辐射的首要靶点, 其损伤效应备受关注。近年来随着研究的不断深入, 发现线粒体也是电离辐射的重要靶点。线粒体作为人体唯一含有编码DNA的细胞器, 受到电离辐射后发生氧化应激不仅影响细胞的正常功能, 甚至导致细胞凋亡。笔者通过现有的研究数据总结了受到电离辐射后线粒体功能和形态的变化, 从而为辐射防护提供新的思路。Abstract: The radiobiology hypothesis is widely accepted by people that damage to the nuclear DNA is the main cause for the effects of radiation. However, some studies shown that the extranulear radiation effects are also very important, especially for mitochondria which contains the coding DNA and important proteins. Mitochondria plays a very important role in oxidative stress and cell death after irradiation. Some experiments present the effects of ionizing radiation on the mitochondria. Here, we discussed the ionizing radiation how to influence the mitochondria. And authors summary some available research data that specific protection of mitochondria could reduce damage to healthy cells exposed to ionizing radiation.
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Key words:
- Radiation, ionizing /
- Mitochondria /
- Oxidative stress
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