灵芝酸A对人肝癌细胞的辐射增敏效应的初步研究

本研究旨在初步探讨灵芝酸A(GAA)对人肝癌细胞系HepG2在高LET中子和低LET的γ射线条件下的辐射敏感性的影响及差异。研究中,我们用CCK-8方法检测不同浓度GAA对HepG2增殖抑制作用。选取低浓度(5μmol/L)GAA预处理细胞24 h,分别给予不同剂量的中子辐照或γ射线辐照,分别检测克隆存活率、细胞凋亡和γH2AX蛋白的foci的形成。结果表明:在不加GAA的情况下,高LET中子辐射比低LET的γ射线对细胞产生的凋亡比例高;在添加了GAA后,与未加GAA对照组相比,诱导细胞凋亡的比例明显增加;另外,加GAA处理后,细胞增殖抑制率也随着辐照剂量的增加而增高。即GAA能增加HepG2细胞的辐射敏感性,而在同样GAA剂量下,HepG2细胞对高LET中子辐射比低LET的γ射线更敏感。由此,这项研究说明灵芝酸或可开发成为一种天然辐射增敏剂,从而为癌症特别是肝癌的放疗提供新的辅助治疗方法。     

12C和X射线辐照人肺癌细胞H1299的生物学效应

用高传能线密度（LET）的12C离子束和低LET的X射线辐照体外培养的非小细胞肺癌H1299(p53基因缺失), 研究它们的辐照生物学效应的差异。 用克隆形成率法测定了细胞对射线的辐射敏感性; 用AnnexinV/PI试剂盒检测了细胞早期凋亡; 用流式细胞仪检测了细胞周期变化。 实验结果表明, 12C离子束辐照H1299细胞的存活率明显低于用X射线辐照的; 12C离子束引起H1299细胞的早期凋亡率明显高于X射线辐照引起的, 且持续时间更长; 12C离子束引起的H1299细胞G2/M期的抑制更明显。 说明H1299细胞对高LET的12C离子束的辐射敏感性高于对X射线的, 重离子对p53基因缺失型肿瘤的治疗可实施较低的照射剂量、 较少的照射次数和较长的时间间隔。     

^12C和X射线辐照人肺癌细胞H1299的生物学效应

用高传能线密度（LET）的^12C离子束和低LET的X射线辐照体外培养的非小细胞肺癌H1299（p53基因缺失）,研究它们的辐照生物学效应的差异。用克隆形成率法测定了细胞对射线的辐射敏感性;用AnnexinV/PI试剂盒检测了细胞早期凋亡;用流式细胞仪检测了细胞周期变化。实验结果表明,^12C离子束辐照H1299细胞的存活率明显低于用X射线辐照的;^12C离子束引起H1299细胞的早期凋亡率明显高于X射线辐照引起的,且持续时间更长;^12C离子束引起的H1299细胞G2/M期的抑制更明显。说明H1299细胞对高LET的^12C离子束的辐射敏感性高于对X射线的,重离子对p53基因缺失型肿瘤的治疗可实施较低的照射剂量、较少的照射次数和较长的时间间隔。     

Survivin表达在高LET射线诱导细胞凋亡中作用机理的初步研究

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LETC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。     

碳离子束混合LET辐照的EBT3辐射变色胶片剂量修正方法

针对EBT3辐射变色胶片对碳离子束混合LET辐照的剂量欠响应比较了两种剂量修正方法。利用260 MeV/u的碳离子束通过被动降能得到多种剂量平均LET的碳离子束,利用这些碳离子束进行了胶片剂量响应刻度辐照,选择最佳的拟合公式得到了胶片剂量刻度曲线。使用RE(Relative Efficiency)量化了EBT3胶片随LET的剂量欠响应,并使用RE剂量修正法修正了混合LET辐照胶片的剂量。此外,根据剂量刻度曲线公式中拟合参数随不同LET所占剂量比例的变化规律,提出了拟合参数剂量修正法并修正了混合LET辐照胶片的剂量。最后比较了这两种方法的结果,表明拟合参数方法得到的剂量偏差在5%以内,优于RE方法10%以内的剂量偏差。     

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.     

不同LET碳离子束辐照拟南芥干种子的当代损伤效应

本研究以拟南芥（Columbia野生型）干种子为材料,利用兰州重离子研究装置（HIRFL）产生的碳离子束对材料进行辐射处理,统计其存活率、根长、下胚轴长及每果荚种子数,以探讨不同传能线密度（Linear Energy Transfer,LET）的碳离子束辐照对拟南芥当代损伤效应的影响。结果表明,在相同LET辐射条件下,随着辐射剂量的增大,拟南芥的存活率、根长、下胚轴长度、每果荚种子数都呈现下降趋势。在相同剂量不同LET辐射处理情况下,随着LET的增大,存活率、根长、下胚轴长、每果荚种子数都显著下降,可见高LET辐射严重抑制了拟南芥的生长和发育。研究表明,当LET为50 keV/μm时,碳离子束辐射拟南芥干种子对应的最佳诱变剂量为200 Gy,为后续开展碳离子束辐射的诱变效率研究奠定了前期基础。Aimed to study the biological effects of carbon ion beams with different linear energy transfer (LET) values provided by Heavy Ion Research Facility in Lanzhou (HIRFL), dry seeds of Arabidopsis thaliana (Columbia-WT) were irradiated and a series of biological effects of postembryonic development, such as survival rate, primary root length, hypocotyls length and number of seeds per silique, were investigated. The results showed that, under the radiation condition of the same LET value, the survival rate, root length, hypocotyls length and number of seeds per silique were decreased with the increasing dose. In addition, under the radiation conditions with different LET values, but same dose, the extent of the decline of the survival rate, root length, hypocotyls length and number of seeds per silique were reinforced with the increasing LET. It was also found that high LET radiations inhibited the subsequent growth and development of Arabidopsis thaliana severely. In brief, it was suggested that the optimum dose of carbon ion beam with 50 keV/μm value on Arabidopsis thaliana dry seeds was 200 Gy. This research complemented the preliminary theoretical foundation for the comparative study of the highest mutation efficiency of carbon ion beam irradiations at IMP, CAS(Institute of Modern Physics, Chinese Academy of Sciences).     

碳离子辐照细胞的相对生物学效率

研究了传能线密度(LET)≥125.5keV/μm的碳离子辐照小鼠黑色素瘤B16、人的宫颈癌HeLa、中国仓鼠肺V79、人的肝癌SMMC-77214种细胞的相对生物学效率(RBE).得到了当LET=125.5keV/μm时,RBE依赖于细胞种类并随细胞存活水平的升高而增加的关系,以及当LET≥125.5keV/μm时,RBE随着LET的增大而变小的关系.     

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.     

一种实验确定微电子器件灵敏体积的方法

介绍一种实验确定微电子器件单粒子翻转(SEU)灵敏体积(S_V)厚度d的方法.用从低到高不同能量的重离子辐照微电子器件, 测量其SEU截面随离子射程的变化曲线σ_seu(r), 用数学计算从σ_seu(r)和LET(r)函数提取d. 利用测得的d和σ_seu(LET), 经过模型计算可得到更精确的空间SEU率的预言值.     

不同LET射线对细胞的生物学效应

以人肝癌细胞系和正常肝细胞系为材料,报道了不同传能线密度射线辐射引发细胞染色体原初断裂及24 h内的修复情况。 计算了相对生物学效应的值。 以L02染色体总断裂数量得出的RBE值96.05 keV/μm的12C6+ 为3.6, 512 keV/μm 36Ar18+ 为2.9。 而以7721染色体总断裂数量得出的RBE值: 96.05 keV/μm的12C6+ 为3.5,512keV/μm 36Ar18+也为2.9。用产生等点染色单体断裂计算,则RBE更高。对比得出,高LET对增加等点染色单体断裂量的作用要远远大于对增加染色单体断裂量的作用。等点染色单体的断裂修复难度要远远大于染色单体断裂的修复难度, 这也是高LET高致死率的一个重要原因。 Human hepatoma SMMC 7721 and normal liver L02 cells were irradiated with γ rays,12C6+ and 36Ar18+ ion beams at the Heavy Ion Research Facility in Lanzhou(HIRFL). We reported the kinetic repair of chromosome breaks of L02 and SMMC 7721 cells in 24 h of post irradiation time. The relative biological effectiveness(RBE) for inducing chromatid breaks were 3.6 for L02 and 3.5 for SMMC 7721 cell lines at the linear energy transfer(LET) peak of 96.55 keV/μm 12C6+ ions, and 2.9 (both of the two cell lines) at 512 keV/μm 36Ar18+ ions.It suggested that the RBE of isochromatid type breaks induced by 36Ar18+ was higher than those by 12C6+. We concluded that the high production of isochromatid type breaks, induced by the densely ionizing track structure, could be regarded as a signature of high LET radiation exposure.     

The High Energy X-ray telescope (HE) onboard the Insight-HXMT astronomy satellite

The Insight-Hard X-ray Modulation Telescope(Insight-HXMT) is a broadband X-ray and γ-ray(1-3000 ke V) astronomy satellite. One of its three main telescopes is the High Energy X-ray telescope(HE). The main detector plane of HE comprises 18 Na I(Tl)/Cs I(Na) phoswich detectors, where Na I(Tl) is used as the primary detector to measure ~ 20-250 ke V photons incident from the field of view(FOV) defined by collimators, and Cs I(Na) is used as the active shielding detector to Na I(Tl) by pulse shape discrimination. Additionally, Cs I(Na) is used as an omnidirectional γ-ray monitor. The HE collimators have a diverse FOV,i.e. 1.1°×5.7°(15 units), 5.7°×5.7°(2 units), and blocked(1 unit). Therefore, the combined FOV of HE is approximately5.7°×5.7°. Each HE detector has a diameter of 190 mm resulting in a total geometrical area of approximately 5100 cm2, and the energy resolution is ~15% at 60 ke V. For each recorded X-ray event by HE, the timing accuracy is less than 10 μs and the deadtime is less than 10 μs. HE is used for observing spectra and temporal variability of X-ray sources in the 20-250 ke V band either by pointing observations for known sources or scanning observations to unveil new sources. Additionally, HE is used for monitoring the γ-ray burst in 0.2-3 Me V band. This paper not only presents the design and performance of HE instruments but also reports results of the on-ground calibration experiments.     

Measurement of LET distribution and dose equivalent on board the space shuttle STS-65

Space radiation dosimetry measurements have been made on board the Space Shuttle STS-65 in the Second International Microgravity Laboratory (IML-2). In these measurements, three kinds of detectors were used; one is a newly developed active detector telescope called “Real-time Radiation Monitoring Device (RRMD)” utilizing silicon semi-conductor detectors and others are conventional detectors of thermoluminescence dosimeters (TLDs) and CR-39 plastic track detectors. Using the RRMD detector, the first attempt of real-time monitoring of space radiation has been achieved successfully for a continuous period of 251.3 h, giving the temporal variations of LET distribution, particle count rates, and rates of absorbed dose and dose equivalent. The RRMD results indicate that a clear enhancement of the number of trapped particles is seen at the South Atlantic Anomaly (SAA) without clear enhancement of dose equivalent, while some daily periodic enhancements of dose equivalent due to high LET particles are seen at the lower geomagnetic cutoff regions for galactic cosmic ray particles (GCRs). Therefore, the main contribution to dose equivalent is seen to be due to GCRs in this low altitude mission (300 km). Also, the dose equivalent rates obtained by TLDs and CR-39 ranged from 146.9 to 165.2 μSv/day and the average quality factors from 1.45 to 1.57 depending on the locations and directions of detectors inside the Space-lab at this highly protected orbit for space radiation with a small inclination (28.5°) and a low altitude (300 km). The LET distributions obtained by two different detectors, RRMD and CR-39, are in good agreement in the region of 15–200 keV/mm and difference of these distributions in the regions of LET < 15 keV/mm and LET > 200 keV/mm can be explained by considering characteristics of CR-39 etched track formation especially for the low LET tracks.     

高效液相色谱法测定杀虫剂灭幼脲三号的含量

本文采用 Hypersil- ODS2 ( 4 .6mm× 2 50 mm,5μm)柱 ,乙腈 -水 - N,N-二甲基甲酰胺 ( 60∶ 4 0∶ 0 .1)为流动相 ,测定波长为 2 54nm,建立了测定灭幼脲三号的高效液相色谱法。该法线性范围为 2 .0— 80μg/m L,回归方程为 A=52 .4 1C+0 .1936,相关系数 r=0 .9987,精密度为 3.5% ( n=11,C=4 0μg/m L) ,检出限为 0 .0 5μg/m L。平均回收率在 96%— 10 4 %之间 ,已用于 2 5%水剂样品的测定 ,结果令人满意。     

Numerical simulation and design of a thermionic electron gun

This paper reports the simulation of an electron gun. The effects on the beam quality of some parameters on the beam quality were studied and optimal choices were identified. It gives numerical beam qualities for a common electrostatic triode gun, and the dependencies on design parameters such as electrode geometries and bias voltages to these electrodes are shown. An electron beam of diameter 5 mm with energy of 5 ke V was assumed for the simulation process. Some design parameters were identified as variable parameters in the presence of space charge.These parameters are the inclination angle of emission electrode, the applied voltage to the focusing electrode, the gap width between the emission electrode and the focusing electrode and the diameter of the focusing electrode. The triode extraction system is designed and optimized by using CST software(for Particle Beam Simulations). The physical design of the extraction system is given in this paper. From the simulation results, it is concluded that the inclination angle of the emission electrode is optimized at 22.5?, the applied voltage to the focusing electrode was optimized and found to be Vfoc =-600 V, the optimal separation distance(gap between emission electrode and focusing electrode) is 4 mm, and the optimal diameter of the emission electrode is 14 mm. Initial results for these efforts aimed at emittance improvement are also given.     

Mutagenic effect of accelerated heavy ions on bacterial cells

The heavy ion accelerators of the Joint Institute for Nuclear Research were used to study the regularities and mechanisms of formation of different types of mutations in prokaryote cells. The induction of direct (lac⁻, ton B⁻, col B) mutations for Esherichia coli cells and reverse his⁻ → His⁺ mutations of Salmonella typhimurium, Bacillus subtilis cells under the action of radiation in a wide range of linear energy transfer (LET) was studied. The regularities of formation of gene and structural (tonB trp-) mutations for Esherichia coli bacteria under the action of accelerated heavy ions were studied. It was demonstrated that the rate of gene mutations as a function of the dose under the action of Γ rays and accelerated heavy ions is described by linear-quadratic functions. For structural mutations, linear “dose-effect” dependences are typical. The quadratic character of mutagenesis dose curves is determined by the “interaction” of two independent “hitting” events in the course of SOS repair of genetic structures. The conclusion made was that gene mutations under the action of accelerated heavy ions are induced by δ electron regions of charged particle tracks. The methods of SOS chromotest, SOS lux test, and λ prophage induction were used to study the regularities of SOS response of cells under the action of radiations in a wide LET range. The following proposition was substantiated: the molecular basis for formation of gene mutations are cluster single-strand DNA breaks, and that for structural mutations, double-strand DNA breaks. It was found out that the LET dependence of the relative biological efficiency of accelerated ions is described by curves with a local maximum. It was demonstrated that the biological efficiency of ionizing radiations with different physical characteristics on cells with different genotype, estimated by the lethal action, induction of gene and deletion mutations, precision excision of transposons, is determined by the specific features of energy transfer of the radiations that affect the character of induced DNA damage, and the efficiency inducible and constitutive cell repair systems. The growth of relative biological efficiency of heavy charged particles is determined by the growth of the damage yield of the DNA participating in the formation of radiation-induced effects, and higher efficiency of inducible repair systems. It was established that the LET value (L _max) for which the maximum (according to the applied irradiation criteria) coefficients of relative biological efficiency are observed varies depending on the character of the registered radiation induced effect. It was demonstrated that for gene mutations and induction of precision excision of mobile elements the values of L _max are realized in a LET range of ≈20 keV/μm. For lethal effects of irradiation and induction of deletion mutations the value of L _max is ≈ 100 and 50 keV/μm, respectively. The differences in the L _max for the studied radiation gene effectis are determined by the different type of DNA damage participating in the mutation process. A molecular model of the formation of gene mutations in Escherichia coli cells under the action of ionizing radiation was proposed. Basic DNA radiation damage and main repair ways were considered in the framework of this model. The basis is the idea of the decisive role of mutagenic, error-prone, branch of SOS repair in fixing premutation DNA damage into point mutations. It was demonstrated that the central mechanism in this process is the formation of an inducible multi-enzymatic complex including the DNA polymerase V (Umu C), RecA-protease, SSB proteins, subunits of DNA polymerase III, performing erroneous DNA synthesis on the damaged matrix. A mathematical model of induction of gene mutations under ultraviolet cell irradiation was developed based on the molecular model.     

FPGA配置片反熔丝PROMs加速器地面单粒子效应特性研究

针对0.13 μm CMOS（Complementary Metal-Oxide-Semiconductor）体硅外延工艺下FPGA（Field Programmable Gate Arrays）配置片反熔丝PROM（Programmable-Read-Only-Memory）进行了单粒子效应（Single Event Effects SEEs）的加速器地面模拟试验研究。以PROM的存储容量、数据类型和工艺差异性为研究变量,考核与验证其在不同种类和能量粒子入射的系列性加速器地面SEEs模拟试验。研究结果表明,相对于8 Mbits PROM而言,空片16 Mbits PROM抗辐射性能最优,且从翻转饱和截面上说,16 Mbits的PROM具备更高的可靠性,优于国外同系列的芯片类型,试验用PROM芯片的单粒子锁定阈值>99.0 MeV·cm2/mg。另一方面,研究0.13 μm CMOS普通与深阱工艺技术下PROM芯片单粒子翻转效应异同性的实验数据表明,在高LET（Linear Energy Transfer）处的两者抗辐射性能并无明显变化,但是低LET处（LET翻转阈值）的加固效果较为明显,即抗辐射技术能力主要体现在LET翻转阈值的提升而非翻转截面的减小。Single event effects (SEEs) have been characterized and investigated on one-time configured devices for field-programmable-gate-arrays (FPGA) of programmable-read-only-memory (PROM) in 0.13 μm Complementary Metal-Oxide-Semiconductor (CMOS) technology.The variables of their memory size,written data and technology have been taken into consideration as the key parameters affecting the SEEs sensitivity when testing and verifying the reliability/radiation tolerance on self-made PROMs by heavy ions.The results show that,16 Mbits PROM within blanked data has been studied that it has better performance to radiation tolerance as compared with the 8 Mbits PROMs.Additionally,16 Mbits PROMs have the higher reliability,if based on the viewpoint of the saturated single event upset cross-section.To the single event latchup,16 Mbits PROMs were exposed to a total fluence of 107 ions/cm2 at the linear energy transfer (LET) of 99.0 MeV·cm2/mg and no obvious fluctuation of current has been observed.Additionally,as comparing the zone of high LET value,0.13 μm CMOS transistors with deep-well technology present a better radiation hardened approach than normal technology,especially in improving the threshold of LET at the zone of low LET value.     

The Low Energy X-ray telescope (LE) onboard the Insight-HXMT astronomy satellite

The Low Energy X-ray telescope(LE) is one of the three main instruments of the Insight-Hard X-ray Modulation Telescope(Insight-HXMT). It is equipped with Swept Charge Device(SCD) sensor arrays with a total geometrical area of 384 cm^2 and an energy band from 0.7 to 13 ke V. In order to evaluate the particle induced X-ray background and the cosmic X-ray background simultaneously, LE adopts collimators to define four types of Field Of Views(FOVs), i.e., 1.6°×6°, 4°×6°, 50°-60°×2°-6 oand the blocked ones which block the X-ray by an aluminum cover. LE is constituted of three detector boxes(LEDs) and an electric control box(LEB) and achieves a good energy resolution of 140 e V@5.9 ke V, an excellent time resolution of 0.98 ms, as well as an extremely low pileup(<1%@18000 cts/s). Detailed performance tests and calibration on the ground have been performed,including energy-channel relation, energy response, detection efficiency and time response.     

Effects of target fragmentation on evaluation of LET spectra from space radiations: implications for space radiation protection studies

We present calculations of linear energy transfer (LET) spectra in low earth orbit from galactic cosmic rays and trapped protons using the HZETRN/BRYNTRN computer code. The emphasis of our calculations is on the analysis of the effects of secondary nuclei produced through target fragmentation in the spacecraft shield or detectors. Recent improvements in the HZETRN/BRYNTRN radiation transport computer code are described. Calculations show that at large values of LET (> 100 keV/μm) the LET spectra seen in free space and low earth orbit (LEO) are dominated by target fragments and not the primary nuclei. Although the evaluation of microdosimetric spectra is not considered here, calculations of LET spectra support that the large lineal energy (y) events are dominated by the target fragments. Finally, we discuss the situation for interplanetary exposures to galactic cosmic rays and show that current radiation transport codes predict that in the region of high LET values the LET spectra at significant shield depths (> 10 g/cm² of Al) is greatly modified by target fragments. These results suggest that studies of track structure and biological response of space radiation should place emphasis on short tracks of medium charge fragments produced in the human body by high energy protons and neutrons.