在DNA损伤修复信号传导通路中ATM介导的BCA1及RAD51作用机理的研究

为阐明毛细血管扩张性共济失调突变基因(Ataxia telangiectasia mutated,ATM)介导的乳癌基因1(Breast cancer gene 1,Brca1)磷酸化及其下游DNA修复相关蛋白(DNA damage repair protein 51,RAD51)在DNA损伤修复信号传导通路中作用机理,以源于正常人皮肤的成纤维细胞系GM细胞(Originated from human skinfibroblast GM Cell,GM0639)为对照,用免疫共沉淀与Western blot方法,观察60Co γ射线照射后共济失调症(Ataxia telangiectasia,AT)细胞、ATM转染的AT细胞(ATM+-AT)和GM细胞的BRCA1及RAD51蛋白表达的变化.经0、5、10、20Gy辐照后,AT细胞通过免疫共沉淀及Western Blot法分析其中ATM和BRCA1蛋白以及BRCA1和RAD51蛋白之间的相互作用以及PI3K抑制剂对ATM磷酸化其下游基因的影响.0Gy照射ATM+-AT和GM细胞未出现BRCA1表达条带;照射后,GM细胞、ATM细胞BRCA1和RAD51蛋白均有表达,而AT细胞无表达;PI3K抑制剂Wortmannin对经电离辐射照射后的AT、ATM+-AT和GM细胞中BRCA1蛋白表达具有抑制作用;照射后ATM+-AT和GM细胞中BRCA1和RAD51蛋白均有表达.因此,电离辐射照射后,BRCA1由ATM介导磷酸化后可进一步与RAD51相互作用,这是信号通路传导过程中的一个级联反映,从而修复损伤的DNA,保持基因组的稳定性.     

用HPRT基因突变及CBMN研究AT细胞高辐射敏感性

研究了毛细血管扩张性共济失调症(Ataxia?telangiectasia,AT)患者皮肤的成纤维细胞系AT5BIVA(AT细胞)的高辐射敏感性。以源于正常人皮肤的成纤维细胞系GM0639(GM细胞)为对照,利用次黄嘌呤磷酸核糖转移酶基因(Hypoxanthinephospho?ribosyltransferase,hprt)位点突变分析技术及胞质分裂阻滞微核法(Cytokinesis?Blockmicronucleusmethod,CBMN),在AT细胞和GM细胞经Coγ射线0、1、2、3、4Gy60照射后,观察比较AT细胞和GM细胞之间hprt基因位点突变频率(hprtMF)、微核率(MNF)及微核细胞率(MNCF)的差异,并分别进行曲线拟合。在各剂量点,AT细胞hprt基因突变频率、微核率及微核细胞率均明显高于GM细胞,其差别具有显著性统计意义(p<0.01);AT和GM细胞hprt基因突变频率、微核率及微核细胞率均与照射剂量呈正相关,可拟合成剂量效应直线方程y=a bx。结果表明,毛细血管扩张性共济失调症患者AT细胞辐射敏感性显著高于GM细胞,具有高辐射敏感性。     

60Coγ射线对AT细胞SOD活性和MDA含量的影响研究

研究毛细血管扩张性共济失调症（AT）患者皮肤的成纤维细胞系AT5BIVA（AT细胞）的应对电离辐射导致细胞氧化损伤的能力。以源于正常人皮肤的成纤维细胞系GM063（GM细胞）为对照,采用超氧化物歧化酶（Superoxide dismutase,SOD）、丙二醛（Malondialdehydc,MDA）测定试剂盒,AT细胞和GM细胞经60^Coγ射线0、1、2、3、4Gy照射后,观察比较它们的SOD活性和MDA含量的差异,并分别进行曲线拟合。结果显示在1、2、3、4Gy剂量照射下,AT和GM细胞中SOD活性均随受照剂量增加而明显降低（P〈0．01）,同一剂量点的AT细胞中SOD活性明显低于GM细胞（P〈0．05）;AT和GM细胞中MDA含量均随受照剂量增加而升高（P〈0．05）,同一剂量点的AT细胞中MDA含量明显高于GM细胞（P〈0．05）。AT细胞和GM细胞的SOD活性和MDA含量均与照射剂量呈线性关系。结果表明由于AT细胞中SOD活性降低,导致AT细胞应对辐射的氧化损伤能力不足,引起AT细胞中MDA含量增加,是AT细胞高辐射敏感性的原因之一。     

DAB2IP基因沉默引起的前列腺癌细胞辐射耐受与ATM的相关性研究

实验以具有不同卵巢癌差异表达基因2相互作用蛋白(Disabled homolog 2 interaction protein,DAB2IP)表达的前列腺癌细胞为研究对象,讨论DNA损伤修复关键蛋白-共济失调毛细血管扩张症基因突变(Ataxia-telangiectasia mutated,ATM)在DAB2IP影响肿瘤细胞放射敏感性中的作用。研究比较了单纯γ-射线(0、2、4、6、8 Gy)和ATM特异性抑制剂-KU55933(10μmol/L)联合射线作用后,不同DAB2IP表达的前列腺癌细胞集落形成率的差异;采用q RT-PCR及Western blot方法分别检测了2 Gy和KU55933+2 Gy照射后,细胞内ATM在翻译转录、蛋白表达和磷酸化水平的变化。结果显示,同一吸收剂量下,DAB2IP基因沉默的前列腺癌细胞,集落形成能力明显高于DAB2IP阳性表达的对照组细胞,并伴随着ATM合成与磷酸化水平的升高。KU55933通过抑制ATM的翻译转录与蛋白磷酸化,可显著增强射线对低表达DAB2IP的辐射耐受细胞的损伤作用。提示ATM是DAB2IP基因沉默引起肿瘤细胞辐射耐受的关键分子,可以ATM为靶点筛选药物,提高DAB2IP基因缺陷的肿瘤患者对放射治疗的敏感性。     

应用单细胞微凝胶电泳技术检测成纤维细胞的放射敏感性

应用单细胞微凝胶电泳（SCGE）技术以及噻唑蓝（MTT）比色法检测辐射诱发的成纤维细胞系AT5BIVA和GM637的初始DNA双链断裂数及断裂拍的修复与细胞放射敏感性之间的关系。结果表明,AT5BIVA细胞系的放射敏感性显著高于GM637。两种细胞系的初始DNA双链断裂数均随剂量的增加而增加,呈显著的剂量效应关系,在给定的剂量点,辐射诱发的AT5BIVA细胞系的初始DNA双链断裂数显著高于GM637。AT5BIVA纱对辐射诱发的DNA双链断裂的修复能力小于GM637。结果提示,辐射诱发的初始DNA双链断裂数及断裂后的修复与细胞的放射敏感性均有一定的相关性,作为细胞放射敏感性预测指标具有很大的应用潜势。     

咖啡因联合辐射处理对人乳腺癌易感基因BRCA1表达的影响

研究了咖啡因对碳离子束辐射的增敏效应,并观察在该过程中人乳腺癌易感基因BRCA1表达的变化。碳离子束联合咖啡因处理人乳腺癌细胞MCF-7后,利用实时细胞检测仪观察细胞生长、流式细胞术检测细胞周期分布变化、real-timePCR检测BRCA1mRNA水平、Westernblot检测BRCA1蛋白水平及其磷酸化水平。结果显示：咖啡因处理导致细胞生长明显受到抑制;咖啡因废除了辐射诱导的G2期阻滞,抑制了BRCA1mRNA和蛋白表达水平,同时特异性抑制了BRCA1的丝氨酸1524位点的磷酸化作用。这些结果表明咖啡因抑制了BRCA1蛋白和其磷酸化表达水平。     

X射线辐照诱导人神经胶质瘤细胞DNA双链损伤研究

采用免疫荧光染色法检测X射线诱导M059K细胞磷酸化组蛋白H2AX(γH2AX)和磷酸化的毛细血管扩张性共济失调症突变基因(pATM)焦点的形成;流式细胞仪分析M059K细胞γH2AX和pATM表达的周期依赖性。免疫荧光染色检测结果显示,γH2AX和pATM焦点阳性细胞分别以照射后0.5、4 h表达最高,照射后24h,高剂量组焦点阳性细胞达100%。流式细胞仪分析结果显示,γH2AX和pATM的表达具有细胞周期依赖性。照射后0.5、4 h,γH2AX和pATM在细胞各期的表达均明显增加,并以G0/G1期为著;照射后24 h,γH2AX和pATM在G0/G1和S期表达降低,而G2/M期细胞表达明显增加。细胞呈现明显的G2/M期阻滞。结果提示,γH2AX和ATM信号通路参与X射线诱导的M059K细胞DNA双链断裂。     

12C^6＋离子束诱导HeLa细胞DNA损伤效应

本文研究了HeLa细胞经过12C^6＋离子柬辐照之后的DNA损伤效应,及辐照后p53激活的分子机制。运用中性单细胞电泳技术,检测了HeLa细胞经过4Gy12C6＋离子束辐照间隔0、3、6和12h之后DNA的损伤情况,及0.5、1、2和4Gy12C^6＋离子束辐照后即时的DNA损伤情况。同时运用细胞生长实时监测仪监测了HeLa细胞在经过0、0．5和1Gy也C6＋离子束辐照之后的生长变化,并运用AO／EB双染检测了辐照细胞24h后的凋亡情况。另外,利用8mmol／L的咖啡因[抑制ATM（ataxia-telangiectasia,mutated）和ATR（ATMand Rad3．relatedkinase）1和20μmol／L的wortmannin[抑制ATM和DNA—PK（DNA-dependent protein kinase）】处理HeLa细胞后再进行1Gy12C^6＋离子束辐照,通过westernblot检测p53的表达。结果显示,12C^6＋离子束辐照可造成HeLa细胞的DNA损伤,损伤随剂量升高而升高但随测定间隔时间降低,诱导HeLa细胞发生凋亡;而且辐照后p53表达升高。结果证明12C^6＋离子束辐照可造成HeLa细胞的DNA损伤并诱导损伤修复及凋亡等效应,损伤效应相关因子p53被激活,并且激活依赖于ATM。     

双标记碱性洗脱法研究电离辐射引起的细胞DNA单链断裂与修复

本文应用双标记碱性洗脱法对X射线照射引起的正常人纤母细胞、毛细血管扩张性共济失调症(AT)纤母细胞、AT肿瘤突变细胞DNA单链断裂及重接修复进行了研究。结果提示10GyX射线照射对三种不同类型纤母细胞DNA的单链断裂与各自的不照射对照组比较有显著差别。而三种不同细胞株之间比较则无明显差别。细胞接受10GyX射线照射后在37℃孵箱中孵育15、30和60min可见三种细胞株DNA单链断裂都能立即进行重接修复,60min内大部分已重接,细胞在10Gy照射后加5×10~(-4)mol/L aphidicolin/皿抑制聚合酶α,经37℃孵育60min也有一定程度的修复。     

Preparation of Zn/TiO2 powder and its photocatalytic performance for oxidation of P-nitrophenol

Zn-doped TiO2 catalysts were prepared using a sol-gel method and characterized by XPS,UV-Vis, BET, XRD in this study. Under the irradiation of simulant sunlight, the photocatalytic activity for the degradation of p-nitrophenol was studied too. After irradiation for 2.5 h, the degradation percentage of p-nitrophenol could rise to more than 80 %. The results showed that the spectrum absorption band edge of Zn/TiO2 powder does not broaden obviously comparing with pure TiO2 powder. Zinc exists as Zn （11）. When calcined at 973 K, there is a new phase as ZnTiO3 in Zn/TiO2 catalyst. The order of photocatalytic activity of Zn/TiO2 catalysts calcined at different temperatures for p-nitrophenol is 773 K 〉 673 K 〉 873 K 〉 573 K 〉 973 K and the photocatalytic activity of Zn/TiO2 catalyst calcined at 773 K is better than TiO2 catalysts heated at the same temperature, and outclasses that of commercial TiO2 catalyst. It also showed that the photocatalytic degradation of p-nitrophenol follows first-order kinetics under the irradiation of simulant sunlight.     

Current status of radiation therapy for prostate cancer

Radiotherapy for the treatment of prostate cancer has been extensively explored in the past. Along with the comprehensive understanding of the biology of prostate cancer and rapid advances in terms of technology, the out- come of treatment for the patients with prostate cancer has improved. The authors review radiotherapy as the primary treatment for the disease, with particular emphasis on the technological advances from both the radiobiological and radiophysics aspects. Nonconventional fractionated irradiation like hyper- or hypo-fractionation has been imple- mented in the clinic, the final results still need to be confirmed in the future. Technological advances like IMRT, IGRT, in the last two decades have significantly improved the delivery of external radiotherapy to the prostate. This has re- sulted in an overall increase in the total dose that can be safely delivered to the prostate, which has led to modest im- provements in the biochemical outcome. However, establishing the standard therapy for prostate cancer remains con- troversial. It is hoped that the next decades will bring continued advances in the development of biologicals that will further improve current clinical outcomes.     

The control system for SSRF injection and extraction

This paper introduces the injection and extraction control system design for SSRF,which is a distributed control system aimed at stability and reliability of the pulse power supplies,PPS(Personnel Protection System)and MPS(Machine Protection System).The hardware environment is mainly based on PLC(Programmable Logic Con- troller),and ARM(Advanced RISC Machine)is also applied for studying stability of the power supplies.WinCC and EPICS(Experimental Physics and Industrial Control System)have been selected as the platforms of SCADA(Super- visory Control and Data Acquisition).For unifying the interfacing to the control computer,all front-end equipments are connected via Industrial Ethemet.     

水平管内含空气蒸汽强制对流冷凝换热模型研究

为研究含空气蒸汽在水平管内强制对流冷凝换热特性,基于对传热传质过程的分析,建立了管内为环状流与波状流条件下的流动冷凝换热模型。从潜热、显热和液膜3个环节对整个换热过程进行建模,最终得到计算局部冷凝换热系数的理论关系式。模型预测结果与实验数据的对比表明,二者相对偏差在±20%以内,验证了该换热模型的准确性与适用性。通过进一步的研究发现：从换热管入口至出口,随着冷凝的进行,管内换热主要热阻由液膜热阻向气液界面的凝结热阻转变;主流气体对流换热过程基本可忽略。     

Investigations on landmine detection by BF3 detector

Experiments were carried out to investigate the possible use of neutron backscattering for the detection of polyethylene (PE) sample buried in the soil. In detection of landmine by neutrons, the neutron detector and its shield play an important role. In this paper, the effects of graphite, heavy water, polyethylene and boric acid moderators on the flux of back scattered neutrons were investigated. We have also experimentally verified the effect of BF3 detector shield and obtained good agreement with theory.     

Web Services interface of SSRF archive data analysis system

Accelerator database stores various static parameters and real-time data of accelerator. SSRF (Shanghai Synchrotron Radiation Facility) adopts relational database to save the data. We developed a data retrieval system based on XML Web Services for accessing the archive data. It includes a bottom layer interface and an interface applicable for accelerator physics. Client samples exemplifying how to consume the interface are given. The users can browse, retrieve and plot data by the client samples. Also, we give a method to test its stability. The test result and performance are described.     

Assessment of radioactivity levels in some oil samples from the western desert, Egypt

Distributions of natural gamma-emitting radionuclides were determined in 93 oil samples collected from some petroleum fields in the western desert of Egypt. The radioisotope activities in the area under investigation lay in the range of (21 ± 4) to (38 ± 13) Bq?L-1 for 226Ra, (9 ± 2) to (15 ± 5) Bq?L-1 for 232Th, and (154 ± 28) to (303 ± 54) Bq?L-1 for 40K. The mean values were 27, 12, and 201 Bq?L-1, respectively. Among oils, variations in radionuclide ac- tivities could be on account of differences in TDS, HCO3, and Ba, with high or low pH. In this environment, oil prop- erties differently affected the mobilization of natural radionuclides. The range of 226Ra variation had been compared with available data from other countries. The calculated absorbed dose rate ranged from 22.33 to 32.66 nGy?h-1 in lo- cation (B) and (E) respectively, which was less than the accepted value.     

Preparation and properties of 117m Sn(IV)-TTHMP in in-vitro and in small animals

In this work,TTHMP was synthesized and labelled with 117m Sn.The preparation conditions,stability and lipophilicity of 117m Sn(IV)-TTHMP were investigated.Biodistribution of the complex in rabbits and mice was studied.It was found that the quantity of TTHMP and pH value of the prepararion solution had vital effects on the labeling yield of 117m Sn(IV)-TTHMP.It was also found that 117m Sn(IV)-TTHMP was hydrophilic and stable at room temperature and 37℃ in open air 117m Sn(IV)-TTHMP showed unexpectedly high bone uptake and bone-to-blood ratio in the animals.This made it potentially useful as an reagent for skeletal scintigraphy and radiotherapy of bone tumors.     

The role of AGFA high-energy CR in the calibration and quality control of multileaf collimators （MLC）

Linear accelerators equipped with multileaf collimators （MLC） are becoming more common and are widely used in the intensity-modulated radiotherapy （IMRT）. There is an imperative need to ensure the commissioning specification of the linear accelerators for the sake of quality assurance （QA） and quality control （QC）. This paper is aimed to investigate the role of AGFA high-energy CR （Computed Radiography） in calibrating dynamic multileaf collimators and evaluating the accuracy of the leaf position. The result shows that AGFA high-energy CR can easily and conveniently be used to calibrate MLC and verify its position. Hence, the application of AGFA high-energy CR is proved to be an accurate and time-saving method for routine MLC QC, especially when MLC calibration adjustments are required.     

Gamma radiation levels in the ambient environment of the QNPP Base

Monitoring results of gamma dose rate level in 1992～2004 in the ambient environment of the Qinshan Nuclear Power Plants(QNPP)Base,the northeast of Zhejiang Province,are reported in this paper.It is shown that the gamma dose rate of five monitoring sites of 2.5 km to QNPP Base is 84～113 nGy/h,with an average of 96 nGy/h in the 13 years.The average value is close to the background level of 93 nGy/h prior to operation of the QNPP Base,and is lower than the monitoring result of 101 nGy/h at the reference site in Hangzhou City.Within 50 km from the QNPP Base,the cumulative dose rate of the thermoluminescent dosimeter(TLD)is 90 nGy/h,which is lower than the back- ground level of 111 nGy/h.