辐射诱发体内旁效应特征的研究进展

大量的细胞生物学研究显示, 辐射诱发旁效应的传输信号包括活性氧自由基（ROS）、 一氧化氮自由基（NO）以及一些细胞因子。 近年来,越来越多的文献报道关于体内旁效应特征的研究, 并已经证实在生物体内辐射诱导的旁效应不仅能发生在相邻组织, 还可发生在远源器官。这些体内旁效应包括DNA损伤、表观遗传学改变、miRNA及基因表达改变、 细胞增殖和凋亡等。 为了总结和分析辐射诱发体内旁效应的特征, 本文综述了辐射诱发体内旁效应的特点, 包括其与性别、 传播途径、辐射品质的关系以及相关机制的研究。 Radiation induced bystander effect is defined as the induction of damage in neighboring non hit cells by signals released from directly irradiated cells. ROS, NO and cytokines are involved in signaling pathways of bystander effects. Recently, the bystander effects in vivo have been reported more and more. It has been indicated that radiation induced bystander effect was localized not only in bystander tissues but also in distant organs. This effect includes many biological endpoints such as DNA damage, epigenetic, miRNA and gene expression changes, cell proliferation and apoptosis. In this review we described different aspects of ionizing radiation induced bystander effects such as its characteristics, sex specific, signaling transfer, dose and LET dependence, and related mechanisms.     

X射线诱导的HeLa细胞旁效应中ROS和NO关系研究

活性氧(ROS)和一氧化氮（NO)是辐射诱导的旁效应信号通路中的两个重要信号分子。 实验研究了这两种信号分子在HeLa细胞旁效应信号通路中的关系。 通过微核实验, 发现X射线辐照过的HeLa细胞及其旁观者细胞微核形成明显增加, 而二甲亚砜（DMSO）预处理显著抑制了微核形成。 另外还发现, 接受条件培养基的旁观者细胞的增殖速率增加, 而DMSO预处理产生条件培养基的受辐照细胞则使旁观者细胞的增殖速率降低。 以上的结果从不同角度证实了HeLa细胞存在X射线诱导的旁效应, 且其可以被DMSO预处理所抑制。Western blotting和DAF FM DA荧光探针检测分别显示出辐照后细胞的诱导型一氧化氮合酶（iNOS）和NO水平均升高, 而DMSO预处理则降低其水平。 因此, 可以推测X射线诱导的HeLa旁效应当中ROS是NO的上游信号。 Accumulating evidence indicates that irradiated cells can release signals which induce a series of biological responses in non exposed cells. This is known as irradiation induced bystander effects. Both reactive oxygen species(ROS) and nitric oxide(NO) play important roles in bystander effects. In this study, we determined the relationship of ROS and NO in the signaling pathway of bystander effects. HeLa cells were treated with or without dimethye sulfoxide(DMSO) before X ray irradiation, and micronuclei formation as well as cell proliferation rate was detected in both irradiated and bystander cells. In addition, we also detected inducible nitric oxide synthase(iNOS) expression and NO level in irradiated cells using Western blotting and DAF FM DA fluorescent probe, respectively. Our results showed that micronuclei were induced in irradiated and bystander cells while DMSO treatment significantly suppressed the formation of micronuclei in both of them. We also found that when cells were irradiated their proliferation rate was suppressed while DMSO treatment eliminated this inhibition effect. In contrast, the cells received conditioned medium from irradiated cells proliferated more quickly than the cells received medium from non irradiated cells while DMSO treatment reduced the difference. Finally, we found that irradiated cells had higher level of iNOS and NO compared to non irradiated controls, whereas DMSO treatment decreased their levels. These results suggest that ROS is the upstream signal of NO in X ray induced bystander effects in HeLa cells.     

聚合物材料的快重离子辐照效应

简要介绍了快重离子辐照损伤的特点,通过与低电离辐射粒子辐照在聚合物材料中产生的效应的类比论述了快重离子辐照在聚合物材料中产生的效应及其研究现状 ,并结合快重离子辐照效应的应用展望了该领域未来的发展.The irradiation effects in polymers induced by swift heavy ions were reviewed in comparison with that induced by low ionization particles based on the characteristics of swift heavy ion irradiations. It is shown that bond breaking and cross linking, gas releasing, amorphization and carbonization of polymers depend strongly on the electronic energy loss. Besides special effects such as alkynes production, can be induced under swift heavy ion irradiation. The perspectives...     

3D组织培养模型及其在辐射诱导旁效应研究中的应用

综述了3D细胞培养技术（TDCC）的发展, 3种主要的体外组织构建方法; 辐射诱导2D细胞产生旁效应的现象与机理; 人工构建的3D组织辐射后诱导的旁效应及其细胞间信号传导机理。 重离子（C离子）辐照作为一种重要的放疗工具, 对其辐射处理3D组织后诱导产生的旁效应进行了展望。 由于3D组织更接近人体细胞生长的真实环境, 因而以3D组织作为模型研究辐射诱导的旁效应, 对于辐射旁效应的防护和治疗可能具有重要的指导意义。 Compared with the cultured monolayer (2D) cells, three dimensional (3D) tissue could be more similar to the environment in vivo including the physical support, chemical factors, cell cell and cell matrix interaction and so on. With the development of three dimensional cell culture techniques (TDCC), 3D tissue is widely used in the areas of bystander effect research. This review focuses on introducing the TDCC method and its application in bystander effect research. First, the development process of 3D tissue culture method was introduced. Secondly, the induction of radiation induced bystander effects both in 2D cell and 3D tissue and its mechanisms were reviewed. Finally, because heavy ion (carbon ion beam) has been developed as a useful tool to cure solid cancer ,and the 3D tissue model is an ideal material to study the damages on body after being irradiated and to understand the underlying mechanisms, future study about heavy ion radiation inducing bystander effect in 3D tissue was discussed.     

空间辐射生物学研究进展

空间电离辐射尤其是高能带电粒子辐射可造成生物机体的严重损伤, 是载人航天飞行的关键性限制因素之一。 研究表明, 带电粒子的生物学效应与其性质、 剂量以及不同生物学终点有关; 此外, 微重力环境可能会影响空间辐射生物学效应。 从多年来的空间搭载实验研究和地基模拟实验研究两个方面, 综述了空间辐射的生物损伤效应及其与微重力环境复合作用的生物效应。Space radiation, particularly induced by the high energy charged particles, may cause serious injury on living organisms. So it is one critical restriction factor in Manned Spaceflight. Studies have shown that the biological effects of charged particles were associated with their quality, the dose and the different biological end points. In addition, the microgravity conditions may affect the biological effects of space radiation. In this paper we give a review on the biological damage effects of space radiation and the combined biological effects of the space radiation coupled with the microgravity from the results of space flight and ground simulation experiments.     

C离子辐照引起细胞分泌旁效应信号因子浓度随时间的变化

信号因子通常能介导旁效应的发生。 利用高LET C离子辐照体外培养的人肝癌QGY-7703细胞, 检测辐照后不同时刻培养基中信号因子TGF-β1和NO的浓度, 并通过转移培养基法检测照射后不同时刻转移培养基对人肝L02旁细胞存活率和代谢活力的影响, 发现受照射细胞在时间与空间上调控着周围信号因子的浓度, 并且通过信号因子浓度的变化影响旁细胞的各种效应发生。 实验为旁效应的解释提供了新的实验数据。 Signaling factors usually play an important role in bystander effect. In this work, human hepatoma QGY 7703 cells in vitro were irradiated with high LET carbon ions. Concentrations of signaling factors such as TGF-β1 and NO were measured in the media of the irradiated QGY-7703 cells at different time points after irradiation. The conditioned media harvested at various times post irradiation were transferred to human hepatocyte L02 cells as bystander cells and then the influence of the conditioned media on survival fraction and cell viability of the bystander cells were determined. The results show that the irradiated cells regulate the concentration of the signaling factors released nearby themselves temporally and spatially, and the bystander cells response to the signaling factors differentially according to the concentration change. This work provides new basic data for exploring the bystander effect, especially caused by high LET radiation.     

Thermodynamic stability of a weakly interactingFermi gas trapped in a harmonic potential

Based on the theoretical results derived from pseudopotential method and local approximation, this paper studies the thermodynamic stability of a weakly interacting Fermi gas trapped in a harmonic potential by using analytical method of thermodynamics. The effects of the interparticle interactions as well as external potential on the thermodynamic stability of the system are discussed. It is shown that the system is stable as for the complete average, but as for local parts, the system is unstable anywhere. This instability shows that the stability conditions of mechanics cannot be satisfied anywhere, and the stability conditions of thermostatics cannot be satisfied somewhere. In addition, the interactions and external potential have direct effects on the local stability of the system.     

Survivin表达在高LET射线诱导细胞凋亡中

先前的研究表明, 肿瘤细胞中survivin的高表达与细胞对高传能线密度(LET)射线的辐射抗性相关。 研究了survivin表达在高LET射线诱导的细胞凋亡中的作用, 发现抑制survivin表达对高LET C离子辐射诱导的Bcl-2和Bax表达没有明显的影响。 在高LET射线辐照中, survivin可能通过抑制caspase-3和-9活性的途径, 抑制了细胞凋亡。It has been proven that over expression of survivin in cancerous cell lines is related to the radioresistance of cells to high LET radiation in previous work. In this study, action mechanisms of survivin gene in apoptosis induced by high LET radiation were investigated. We found that inhibiting survivin by siRNA had no notable influence on Bcl-2 and Bax expressions induced by carbon ions. Survivin depressed cell apoptosis through the inhibition of the activities of caspase-3 and -9 possibly in cell apoptosis induced by high LET radiation.     

60Co gamma radiation effect on AlGaN/AlN/GaN HEMT devices

The testing techniques and experimental methods of the ⁶⁰Co gamma irradiation effect on AlGaN/AlN/ GaN high electron mobility transistors （HEMTs） are established. The degradation of the electrical properties of the device under the actual radiation environment are analyzed theoretically, and studies of the total dose effects of gamma radiation on AlGaN/AlN/GaN HEMTs at three different radiation bias conditions are carried out. The degradation patterns of the main parameters of the AlGaN/AlN/GaN HEMTs at different doses are then investigated, and the device parameters that were sensitive to the gamma radiation induced damage and the total dose level induced device damage are obtained.     

Investigation on nonlinear thermo-acoustic characteristics of Rijke tube

Based on the energy conservation relationship,nonlinear thermo-acoustic effects of Rijke tube including instability range,saturation processes and higher harmonics modes were investigated.With coupling between the external flow and the inner space of a Rijke tube, the acoustic characteristics of self-excited oscillation were simulated.The experimental study was also carried out and the results were compared with those from simulation.The nonlinear factors which distort the acoustic waveform distortion were analyzed.From the results,it is seen that varying size of the nozzle outlet changes the acoustic impedance in the boundary, and leads to reduction of the nonlinear effects.The results show that the modes of self-excited oscillation could be influenced by the position of higher harmonics.In the large amplitude oscillation,the distortion of pressure wave within Rijke tube could be induced by the acoustic losses due to vortices on nozzle.It is found that the waveform distortion could be avoided by the shrinkage of nozzle.     

植物个体远程辐射信号早期传递过程的研究体系创建

自2005年以来,活体中的远程辐射旁效应逐渐成为辐射生物学的研究热点,然而其早期信号传递过程的相关研究却鲜见报道,主要原因是由于早期信号传递过程研究所需的旁区与辐射区的自由分离与组合在动物模型上无法实现。本研究是基于植物个体可以切割和嫁接的特性,借鉴离体细胞培养基转移方法研究旁效应早期过程的思想,在植物个体上实现旁区与辐照区的"分离"与"组合",构建了一种研究个体远程辐射信号早期传递过程的植物实验体系。具体是以模式植物拟南芥菜转基因系(AtRAD54promoter∶∶GUS)为材料,同源重组修复相关基因AtRAD54表达水平为生物学检测终点,人为地将辐照区的组织(或器官)与旁区部分"分离"或"嫁接",通过测定旁区组织(或器官)的AtRAD54基因表达水平变化,研究其辐射信号传递的早期过程。该研究体系的创建为活体旁效应早期过程的研究提供了一种可行的研究方法。     

辐照诱导人正常肝细胞系HL-7702 细胞远后的微卫星不稳定性

采用高传能线密度(LET) 的12C6+离子束和低LET 的X 射线辐照人正常肝细胞系HL-7702 细胞,利用微卫星不稳定性(MSI) 检测来分析直接受照射细胞和通过转移培养基方式旁细胞传代八代子细胞以MSI 表征的远后效应。实验结果表明,12C6+离子束诱导的远后效应较X射线的低;旁细胞的远后效应较直接受照射细胞的高;辐射引起的MSI 与杂合性丢失(LOH) 的发生率具有位点特异性。结果提示,重离子放射治疗较X 射线放射治疗对正常组织引发的辐射风险要小,可通过对MSI 高发位点的筛选来评估放疗后患者长期生存状况和二次癌症发生风险。Human normal liver cell line HL-7702 cells were irradiated with high linear energy transfer (LET) 12C6+ ions and low-LET X-rays, respectively. Delayed effect in terms of microsatellite instability (MSI) in progenies of the directly irradiated cells and bystander cells, obtained in the way of medium transfer at the 8th passage postirradiation,were examined. The delayed effect induced by the high-LET 12C6+ ions was different from that induced by the low-LET X-rays, and a higher incidence of MSI was observed in the progenies of the cells after exposure to the X-rays than to the 12C6+ ions. We also found that the delayed effect in the progenies of the bystander cells was much more severe than thoseof directly irradiated cells. Furthermore, the events of MSI and loss of heterozygosity (LOH) induced by the ionizing radiations were not randomly distributed throughout the genome and specific loci existed indeed. These results imply that the radiation risk to normal tissues is lower in heavy ion therapy than in conventional X-ray radiotherapy, and the analysis of microsatellite loci with MSI high frequency occurrence can be applied to access long-term survival condition and second cancer risk for the patients after radiotherapy.     

微束技术在放射生物学中的应用

微束装置可以为生命科学研究提供微米定位、剂量特定的电离辐射,在生物体内的电离辐射靶物质及其敏感度、靶物质的损伤及修复机制研究中具有独特的作用。概述了生物微束装置和实验技术的发展及其在低剂量辐射效应、旁观者效应、信号传导研究中的主要应用;介绍了中国科学院近代物理研究所（IMP）重离子微束装置,该装置可以提供能量7~ 80 MeV/u、传能线密度为30~ 3000 keV/μm的重离子微束,实现了活细胞辐照和在线观察、小鼠定位辐照的实验技术;利用IMP微束装置在重离子诱导旁效应实验、小鼠下丘脑重离子辐照效应和DNA损伤快速修复动态等方面取得了一些实验成果。The microbeam facility can provide micrometer scale localized and predefined ionizing radiation in the life science study, and the microbeam techniques play a unique role in determining the target substances of ionizing radiation, as well as in the study of radiation sensitivity, mechanisms of radiation damage response and repair. This paper summarizes the technical developments of biological microbeam facilities and their applications in the studies of low-dose radiation effect, bystander effect and cellular signaling. This paper also introduces the recent developments at the heavy-ion microbeam facility in the Institute of Modern Physics (IMP), which can provide heavy ion microbeam irradiation with energy of 7~80 MeV/u and LET of 30~3000 keV/μm. The facility can perform radiobiological irradiation and online investigation in living cells and mice, including bystander effect study, sleeping system influence after irradiation to mice hypothalamus and the recruitment dynamics of XRCC1 protein.     

利用拉曼光谱技术研究低剂量X射线辐射对人神经母细胞瘤细胞的影响

低剂量电离辐射引发的生物效应复杂而多样,其研究往往又受到辐射标志物和检测技术手段的限制。将拉曼光谱技术应用于低剂量辐射生物效应研究,利用10 mW,532 nm共聚焦拉曼光谱对经过100,200和500 mGy三种辐射剂量的X射线辐照之后的人神经母细胞瘤细胞进行检测,发现细胞嘌呤核苷酸（722～728和1 572～1 581 cm-1等等）、嘧啶核苷酸（770～785 cm-1等等）等DNA相关的拉曼特征峰受到电离辐射影响而发生变化,说明低剂量X射线辐照造成细胞DNA水平改变。采用流式细胞术对同样条件辐照后培养6 h的人神经母细胞瘤细胞进行细胞周期分析发现,三种剂量的X射线电离辐射均造成细胞在G2期阻滞,同样提示电离辐射引起DNA水平升高。通过划痕实验分析辐照后20 h的细胞迁移能力,结果显示,相较于未接受X射线照射的对照细胞,受到三种剂量电离辐射的人神经母细胞瘤细胞均出现迁移水平下降。研究结果表明,通过拉曼光谱分析发现低剂量X射线电离辐射引起人神经母细胞瘤细胞DNA水平变化,其结果与细胞周期分析和迁移分析的结果相一致,但检测时间大大提前,利用拉曼光谱技术可以实现低剂量辐射损伤等细胞生物学效应的早期发现与监测。     

辐射感生应力弛豫对AlmGa1－mN/GaN HEMT电学特性的影响

基于电荷控制原理建立了辐射感生Al_mGa_1-mN势垒层应力弛豫对Al_mGa_1-mN/GaN HEMTs器件电学特性影响的解析模型，并进行了仿真分析.结果表明，对于高Al组分HEMTs器件，Al_mGa_1-mN势垒层中辐射感生的应力弛豫影响更为显著.辐射感生应力弛豫不但导致2DEG下降和阈值电压正向漂移，而且能够引起漏极输出电流的明显下降.辐射感生应力弛豫是赝配Al_mGa_1-mN/GaN HEMTs辐射损伤的重要机理之一. 关键词： mGa_1-mN/GaN')" href="#">Al_mGa_1-mN/GaN HEMT 辐射损伤 应力弛豫     

Advances in radiation biology: Radiosensitization in DNA and living cells

One fundamental goal of radiation biology is the evolution of concepts and methods for the elaboration of new approaches and protocols for the treatment of cancers. In this context, the use of fast ions as ionizing particles offers the advantage of optimizing cell killing inside the tumor whilst preserving the surrounding healthy tissues. One extremely promising strategy investigated recently is the addition of radiosensitizers in the targeted tissue. The optimization of radiotherapy with fast ions implies a multidisciplinary approach to ionizing radiation effects on complex living systems, ranging from studies on single molecules to investigations of entire organisms.In this article we review recent studies on ion induced damages in simple and complex biological systems, from DNA to living cells. The specific aspect of radiosensitization induced by metallic atoms is described. As a fundamental result, the addition of sensitizing compounds with ion irradiation may improve therapeutic index in cancer therapy. In conclusion, new perspectives are proposed based on the experience and contribution of different communities including Surface Sciences, to improve the development of radiation biology.