辐射敏感性影响因素研究

辐射敏感性受到许多因素的影响。以生殖细胞损伤、细胞遗传学损伤、细胞凋亡、DNA损伤和修复作为观察终点，结果显示辐射敏感性存在着年龄差别，遗传因素、性别、生活习惯(如吸烟)、小剂量照射等因素对辐射敏感性也存在不同程度的影响。     

重离子与X射线辐照细胞的敏感性比较

离体的肿瘤细胞和正常细胞的固有辐射敏感性的研究表明 ,不论同种组织间还是不同种类组织间 ,它们的敏感性均存在明显差别[1 ] 。在肿瘤的放射治疗中 ,正常组织的敏感性限定着肿瘤的辐射量 ,而肿瘤组织细胞的敏感性又限定着该剂量杀灭肿瘤的程度 ,所以肿瘤及其周围正常组织的固有细胞辐射敏感性的区别很可能是影响肿瘤疗效的重要因素之一。影响辐射敏感性的因素有许多 ,其中 ,包括ＤＮＡ损伤及其修复 ,细胞增殖率及细胞周期不同时相的细胞比例 ,细胞周期的检查点 ,ＤＮＡ含量 ,等等。为此 ,我们研究了重离子与Ｘ射线辐照细胞的敏感性比较。…     

组蛋白修饰影响细胞辐射敏感性的研究进展

组蛋白修饰在细胞DNA损伤修复过程发挥重要作用。近年来多项研究表明,组蛋白修饰可以在参与招募DNA损伤修复因子、创建染色质开放结构和建立组蛋白抑制性标记等方面影响细胞对辐射的应答。同时,调控组蛋白修饰方式可以影响DNA损伤修复的过程,进而影响辐射敏感性。本文就组蛋白修饰影响DNA损伤修复过程与辐射敏感性的机制进行综述。     

DNA组构状态影响细胞辐射敏感性和初始DNA链断裂的测定

评价了中性滤膜洗脱、类核分析、碱解旋等几种测定哺乳类细胞中“初始”DNA损伤的方法,并着重讨论了DNA包装因素而不是DNA分子本身的断裂因素对细胞辐射敏感性以及对这些测定方法的影响。     

异染色质蛋白HP1α参与辐射损伤修复的研究

目的 研究HP1α对辐射损伤修复的影响。方法 用反义技术单独抑制HP1α和联合抑制HR24L表达，观察细胞对辐射敏感性的影响，用免疫共沉淀法观察HP1α是否参与修复蛋白复合物的形成。结果 单独抑制HP1α，细胞对辐射敏感性与正常细胞相比差异无显著性，联合抑制HP1α和HR24L时，细胞对辐射的敏感性比单独抑制HR24L时显著增加；20 Gyγ射线照射后8h，可检测出HR24L与HP1α复合物的存在。结论 HP1α与修复蛋白相互作用，参与DNA损伤修复，从而影响细胞对辐射的敏感性。     

AT细胞对电离辐射敏感原因的探讨

AT细胞具有对电离辐射和拟辐射物质的高敏感性以及DNA合成抑制抗性,存在复杂的基因异质性。本文从AT细胞的遗传学互补性分析、DNA损伤修复缺陷以及DNA拓扑酶学研究三方面对AT细胞辐射敏感性的分子机理等进行了讨论,认为DNA双链路复缺陷与重接忠实性下降可能足AT细胞电离辐射敏感性的原因。     

AT细胞对电离辐射敏感原因的探讨

AT细胞具有对电离辐射和拟辐射物质的高敏感性以及DNA合成抑制市性，存在复杂的基因异质性，本从AT细胞的遗传学互补性分析，DNA损伤修复缺陷以及DNA拓扑酶学研究三方面对AT细胞辐射敏感性的分子机理等进行了讨论，认为DNA双链修复缺陷与重接忠实性下降可能是AT细胞电离辐射敏感性的原因。     

细胞辐射敏感性与DNA双链断裂及修复相关性研究

细胞的辐射敏感性一般由辐照后细胞的存活情况来衡量。细胞的辐射敏感性存在差异，不同个体不同组织来源的细胞对于同种辐射的反应不同，而同种细胞对不同的辐射的反应也存在明显差异。研究表明，DNA是辐射的靶，电离辐射可以引起多种形式的DNA损伤，改变碱基和糖类，引起DNA—DNA和DNA-蛋白之间的交联，同时可以引起DNA单链断裂（single strand break，SSB）和DNA双链断裂（double strand break，DSB）。大量的中性洗脱实验证明DSB是引起细胞死     

DNA损伤修复与细胞凋亡

：细胞ＤＮＡ的损伤修复是影响细胞存活和死亡的主要原因，细胞缺乏修复能力，其辐射敏感性就会增加。近年来，ＤＮＡ损伤修复的机制已被逐步阐明。本文介绍ＤＮＡ损伤修复和细胞凋亡发生的机制及其与细胞周期、细胞增殖关系的研究进展。     

DNA损伤修复与细胞凋亡

细胞ＤＮＡ的损伤修复是影响细胞存活和死亡的主要原因，细胞缺乏修复能力，其辐射敏感性就会增加。近年来，ＤＮＡ损伤修复的机制已被逐步阐明。本文介绍了ＤＮＡ损伤修复和细胞凋亡发生和机制及其与细胞周期、细胞增殖关系的研究进展。     

Comparison of bleomycin and radiation in the G2 assay of chromatid breaks

PURPOSE: To compare bleomycin with radiation in the G2 chromatid break assay. Controversy exists in the literature about whether G2 bleomycin chromatid-break sensitivity links with cancer predisposition in the same way as the G2 chromatid radiosensitivity test (the so-called 'G2 assay'). Although bleomycin is referred to as a 'radiomimetic' agent, it differs from radiation in the way the damage is induced. MATERIALS AND METHODS: Epstein-Barr virus-immortalized lymphoblastoid cell lines from two head and neck squamous cell carcinoma patients, two breast cancer patients, two ataxia-telangiectasia patients and two normal control persons were used. Chromosomal damage was determined in cells exposed to 0.3-Gy radiation or 5 mU ml(-1) bleomycin. The numbers of chromatid breaks per cell and of aberrations per cell (i.e. breaks and gaps) were determined. RESULTS: A strong positive correlation was found between the two different damage inducers (r=0.99; p<0.001). This correlation was similar for both the breaks per cell and the total aberrations per cell. Inclusion of gaps in the scoring of chromatid breaks was associated with a higher variability of the data, but this did not influence the outcome of this study. CONCLUSIONS: Both bleomycin and radiation give the same sensitivity phenotypes as determined by the G2 assay of chromatid breaks. Thus, when no radiation facility is present, bleomycin seems to be a good alternative to radiation for this type of assay.     

Effect of cisplatin on the recovery from sublethal and potentially lethal radiation damage in cell culture

The effect of Cisplatin upon the recovery from sublethal damage during fractionated irradiation and upon the recovery from potentially lethal damage after a single dose has been investigated. In three mammalian cell lines, Cisplatin did not influence the recovery from sublethal and potentially lethal damage. There were differences among the three cell lines in their ability to recover from radiation damage. However, a significant quantitative difference between the recovery from sublethal and potentially lethal damage in any one cell line could not be found.     

STAT3与辐射敏感相关性的研究进展

放疗是肿瘤治疗的主要方法之一, 但肿瘤的辐射抵抗是影响放疗疗效的一个重要原因。信号转导和转录激活因子3(STAT3)是STAT家族的重要成员, 与肿瘤的发生、发展紧密相关。电离辐射可以对STAT3的表达水平产生影响, 同时STAT3的表达水平也可反作用于细胞, 通过对肿瘤细胞DNA损伤、自噬、凋亡、增殖、血管生成、迁移、侵袭、免疫抑制等的调节影响其辐射敏感性, 这预示着以STAT3为突破口的辐射敏感性研究将会为肿瘤临床治疗提供新策略。     

染色质结构影响肿瘤细胞辐射敏感性的研究进展

染色质结构修饰在DNA复制、转录、修复和重组的过程中发挥重要作用。近年来研究表明,染色质结构修饰不仅影响电离辐射后的DNA损伤的产生并且还参与多个DNA损伤反应（DDR）的信号通路。本文就染色质结构及其在DNA损伤修复中的作用,特别是特征性染色质结构、组蛋白修饰对肿瘤细胞辐射敏感性的影响进行了综述。     

电离辐射对线粒体损伤的研究进展

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。     

Comparison of bleomycin and radiation in the G2 assay of chromatid breaks

Purpose: To compare bleomycin with radiation in the G2 chromatid break assay. Controversy exists in the literature about whether G2 bleomycin chromatid‐break sensitivity links with cancer predisposition in the same way as the G2 chromatid radiosensitivity test (the so‐called ‘G2 assay’). Although bleomycin is referred to as a ‘radiomimetic’ agent, it differs from radiation in the way the damage is induced.

Materials and methods: Epstein–Barr virus‐immortalized lymphoblastoid cell lines from two head and neck squamous cell carcinoma patients, two breast cancer patients, two ataxia‐telangiectasia patients and two normal control persons were used. Chromosomal damage was determined in cells exposed to 0.3‐Gy radiation or 5?mU?ml^?1 bleomycin. The numbers of chromatid breaks per cell and of aberrations per cell (i.e. breaks and gaps) were determined.

Results: A strong positive correlation was found between the two different damage inducers (r=0.99; p<0.001). This correlation was similar for both the breaks per cell and the total aberrations per cell. Inclusion of gaps in the scoring of chromatid breaks was associated with a higher variability of the data, but this did not influence the outcome of this study.

Conclusions: Both bleomycin and radiation give the same sensitivity phenotypes as determined by the G2 assay of chromatid breaks. Thus, when no radiation facility is present, bleomycin seems to be a good alternative to radiation for this type of assay.     

The relationship of DNA double-strand break induction to radiosensitivity in human tumour cell lines

Recent data suggest that the differences in radiosensitivity between cell lines can be related to differences in dsb induction (Radford 1986a). In the light of this we have set out to assess the extent to which differences in radiation survival between human tumour cell lines can be attributed to differences in dsb induction. For nine human tumour lines survival was assayed by clonogenic assay and compared with dsb induction by irradiation at ice-bath temperature as measured by neutral filter elution. The lines varied widely in their sensitivity, ranging from a sensitive neuroblastoma (surviving fraction at 2 Gy, SF2 = 0.13) to a resistant bladder carcinoma (SF2 = 0.62). Dsb induction was found to vary between the cell lines, such that resistant cells generally suffered less damage than sensitive ones. However, the relationship between damage induction and cellular sensitivity was not a simple one, and other factors which may influence sensitivity need to be invoked. These data suggest that, in human tumour cell lines, differences in radiosensitivity may at least in part be due to different levels of damage induction, but that some lines may vary in their tolerance of damage due to differences in biological characteristics such as repair capacity.     

Initiation of ionizing radiation-induced apoptosis: DNA damage-mediated or does ceramide have a role?

PURPOSE: To critically review the data supporting membrane damage-induced increases in ceramide levels as the primary initiator of ionizing radiation-induced apoptosis and to point out that there is compelling evidence supporting the involvement of DNA damage in this process. CONCLUSIONS: There is now a significant literature suggesting that irradiation of cells can quickly lead to a modest, transitory increase in the level of the putative second messenger ceramide. These results have been used to support the views that membrane damage is the primary trigger for radiation-induced apoptosis and that DNA damage is irrelevant to this process. It is argued, however, that the data are inadequate to support such conclusions because it is questionable whether the induced levels of ceramide are toxic and because the ceramide hypothesis cannot convincingly explain the delayed apoptosis, dependent on events such as mitosis, that is shown by many cell lines. In contrast, it is suggested that the sensitivity of some cell types to the induction of apoptosis by DNA-targeted radiation damage, the relationship between p53 status and radiation response, and the influence of enzymatic DNA repair capability on susceptibility to apoptosis, argue strongly that DNA damage is relevant to the triggering of apoptosis.     

Functional inactivation of p53 by HPV-E6 transformation is associated with a reduced expression of radiation-induced potentially lethal damage

PURPOSE: To examine the effect of functional loss of p53 on radiation sensitivity and potentially lethal damage repair (PLDR). MATERIALS AND METHODS: Radiation sensitivity and PLDR were examined in an isogenic pair of human tumour cell lines created by HPV-E6 transformation. RESULTS: Inactivation of p53 by E6 transformation resulted in a cell line that was more resistant to killing by radiation but showed little enhancement in survival (PLDR) when plateau-phase cells were held non-cycling after radiation exposure. Holding p53-normal cells in plateau-phase after radiation exposure not only led to enhanced survival, but also to a reduction in the proportion of cells that blocked in G1 subsequent to release. CONCLUSIONS: These results suggest that p53 expression influences that component of radiation sensitivity associated with PLDR.     

The Relationship of DNA Double-strand Break Induction to Radiosensitivity in Human Tumour Cell Lines

Summary

Recent data suggest that the differences in radiosensitivity between cell lines can be related to differences in dsb induction (Radford 1986a). In the light of this we have set out to assess the extent to which differences in radiation survival between human tumour cell lines can be attributed to differences in dsb induction. For nine human tumour lines survival was assayed by clonogenic assay and compared with dsb induction by irradiation at ice-bath temperature as measured by neutral filter elution. The lines varied widely in their sensitivity, ranging from a sensitive neuroblastoma (surviving fraction at 2 Gy, SF₂ = 0·13) to a resistant bladder carcinoma (SF₂ = 0·62). Dsb induction was found to vary between the cell lines, such that resistant cells generally suffered less damage than sensitive ones. However, the relationship between damage induction and celluar sensitivity was not a simple one, and other factors which may influence sensitivity need to be invoked. These data suggest that, in human tumour cell lines, differences in radiosensitivity may at least in part be due to different levels of damage induction, but that some lines may vary in their tolerance of damage due to differences in biological characteristics such as repair capacity.