Effects of low and high LET radiations on bystander human lung fibroblast cell survival

Purpose: This investigation is aimed to determine the role of low LET (linear energy transfer, γ-rays) and high LET (α-particles) radiations on bystander effect of using the same type of cells and its implications on colony-forming efficiency from a single cell.

Materials and methods: Normal human fetal lung (MRC-5), immortalized repair deficient ataxia telangiectasia mutated (ATM) (GM5849C) and normal (GM637H) fibroblast cells were used. Colony-forming efficiency in bystander cells (GM637H) was studied using the medium transfer technique from the two donor (MRC-5 and GM5849C) cells and the procedure followed for bystander treatment is presented schematically in . Evidence of change in colony formation in bystander cells, was assessed by scavenging nitric oxide (NO).

Effects of low and high LET radiations on bystander human lung fibroblast cell survival

All authors

Dr Rajamanickam Baskar, Adayabalam S. Balajee & Charles R. Geard

https://doi.org/10.1080/09553000701384499

Published online:

03 July 2009

Figure 1. Schematic representation of the technical procedure followed for the sham-treated control and bystander cells.     

2.

高 LET 和低 LET 辐射体外诱发细胞恶性转化的比较          下载免费PDF全文

刘国廉  祝霄霞  周淑珍  樊飞跃  杨素霞  普琳  吴德昌 《中华放射医学与防护杂志》1997,17(3):186-188

目的本研究采用体外细胞转化系统，比较观察了高ＬＥＴ（２３８Ｐｕα粒子，５．２５ＭｅＶ）和低ＬＥＴ（Ｘ射线，１８０ｋＶ）辐射体外诱发成年大鼠肺成纤维细胞系（ＷＡＬ－Ｆ１）恶性转化的特点。方法①应用体外细胞转化模型；②观察指标包括转化细胞形态学和生物学特性的改变；③转化细胞在体内的致瘤作用等。结果α粒子和Ｘ射线诱发同一细胞系转化的形态学与生物学特性基本相似，但在生物学效应上二者存在以下的差异：①细胞存活曲线模型，α粒子为单击单靶模型，Ｄ０值为０．１７２Ｇｙ；Ｘ射线为单击多靶模型，Ｄ０值为１．６６Ｇｙ；②对细胞增殖能力、染色体畸变及集落形成率的影响，产生相近的生物效应所需的剂量，α粒子比Ｘ射线约低１０倍；③以在动物体内致瘤性为终点，引发肿瘤的剂量，α粒子对Ｘ射线的ＲＢＥ值为６（３．０／０．５）。结论实验表明，高ＬＥＴ对体外细胞亦具有较高的致瘤效应。     

3.

Differences between biological effects of high LET and low LET radiations in relation to their application in radiotherapy     

G W Barendsen 《Radiologia clinica》1977,46(5):380-389

The application of fast neutrons, negative pions or heavy ions will only provide an advantage for the radiotherapy of cancer if, in comparison with conventional radiation, e.g., X-rays, gamma rays and electrons, better depth-dose and collimation characteristics or specific radiobiological dose-response relationships result in greater local control probabilities for tumours without increased frequencies of severe normal tissue damage. Differences in intrinsic radiosensitivity and the presence of hypoxic cells are considered to be the main factors which can cause values of the relative biological effectiveness (RBE) for responses of tumours to be larger than RBE values for normal tissue tolerance. Clinical studies on lung metastases irradiated with single doses of 15 MeV neutrons indicate that RBE values for tumour growth delay can vary between 1.2 and 4.0, while RBE values for damage to several normal tissues are estimated from data on a few animal tissues to be approximately 2.5.     

4.

Relationship between oocyte apoptosis and ovarian tumours induced by high and low LET radiations in mice     

Nitta Y  Hoshi M 《International journal of radiation biology》2003,79(4):241-250

PURPOSE: To investigate the biological effectiveness of neutrons at the energy below 1 MeV on apoptosis and carcinogenesis in the mouse ovary. MATERIALS AND METHODS: Female mice were exposed to 1.0 Gy monoenergetic neutrons (0.317, 0.525 and 1.026 MeV), (252)Cf fission neutron (2.13 MeV) or (137)Cs gamma-rays at 7 days of age. Apoptosis of the oocyte and pregranulosa cells, and ovarian carcinogenesis were compared between the radiations. The efficiency of gamma-rays for granulosa cell tumorigenesis was tested by transplantation of the irradiated ovaries into non-irradiated mice. RESULTS: The cumulative apoptotic index of oocytes was 77.9%, 65.6% and 41.6% for the 0.525 MeV neutron, 2.13 MeV neutron and gamma-rays, respectively. Follicles with apoptotic pregranulosa cells were 53.0%, 18.3% and 22.8% of cumulative index for the three groups. Tubular adenomas developed in the groups of monoenergetic neutrons (26.1%) and gamma-ray (35.5%), whereas granulosa cell tumours developed only in the gamma-ray groups (3.2% for 1.0 Gy and 15.6% for 3.0 Gy). Partial-body irradiation with 3 Gy gamma-rays to the ovaries induced granulosa cell tumours with an incidence of 27.3%. CONCLUSION: Effectiveness of neutrons to cause apoptosis was higher for 0.525 MeV than for 2.13 MeV. The pregranulosa cell apoptosis occurred in an oocyte-prone manner. The higher effectiveness of neutrons than gamma-rays to induce oocyte and pregranulosa cell apoptosis correlates with the inhibition of granulosa cell tumour development.     

5.

Radiation response of primary human skin fibroblasts and their bystander cells after exposure to counted particles at low and high LET     

Frankenberg D  Greif KD  Giesen U 《International journal of radiation biology》2006,82(1):59-67

PURPOSE: To investigate the dependence of bystander effects on linear energy transfer (LET) in the low dose region. MATERIALS AND METHODS: The single-ion microbeam of the Physikalisch-Technische Bundesanstalt (PTB) was used to irradiate confluent primary human skin fibroblasts. Cells plated on a special irradiation dish were targeted with 10 MeV protons (LET 4.7 keV/microm) and 4.5 MeV a-particles (LET 100 keV/microm). During exposure, the cells were confluent allowing signal transfers through both gap junctions and diffusion. RESULTS: For 10 MeV protons the clonogenic capability was significantly higher after exposure to 70 protons (0.31 Gy) compared with unirradiated cells. For higher doses the survival curve was exponential. Exposure of only 10% of all nuclei resulted in a similar radiation response in the low dose region. For higher doses up to 2.2 Gy no cell killing was observed. For 4.5 MeV alpha-particles an exponential survival curve was obtained. Irradiation of only 10% of all cell nuclei resulted in an survival curve as had been expected in the absence of any bystander effect. CONCLUSION: The type and extent of bystander effects turned out to be dependent on the particles' LET and are likely to depend also on the cell line used and the techniques applied.     

6.

Relationship between oocyte apoptosis and ovarian tumours induced by high and low LET radiations in mice     

Y. NITTA  M. HOSHI 《International journal of radiation biology》2013,89(4):241-250

Purpose : To investigate the biological effectiveness of neutrons at the energy below 1 MeV on apoptosis and carcinogenesis in the mouse ovary. Materials and methods : Female mice were exposed to 1.0 Gy monoenergetic neutrons (0.317, 0.525 and 1.026 MeV), 252 Cf fission neutron (2.13 MeV) or 137 Cs γ-rays at 7 days of age. Apoptosis of the oocyte and pregranulosa cells, and ovarian carcinogenesis were compared between the radiations. The efficiency of γ-rays for granulosa cell tumorigenesis was tested by transplantation of the irradiated ovaries into non-irradiated mice. Results : The cumulative apoptotic index of oocytes was 77.9%, 65.6% and 41.6% for the 0.525 MeV neutron, 2.13 MeV neutron and γ-rays, respectively. Follicles with apoptotic pregranulosa cells were 53.0%, 18.3% and 22.8% of cumulative index for the three groups. Tubular adenomas developed in the groups of monoenergetic neutrons (26.1%) and γ-ray (35.5%), whereas granulosa cell tumours developed only in the γ-ray groups (3.2% for 1.0 Gy and 15.6% for 3.0 Gy). Partial-body irradiation with 3 Gy γ-rays to the ovaries induced granulosa cell tumours with an incidence of 27.3%. Conclusion : Effectiveness of neutrons to cause apoptosis was higher for 0.525 MeV than for 2.13 MeV. The pregranulosa cell apoptosis occurred in an oocyte-prone manner. The higher effectiveness of neutrons than γ-rays to induce oocyte and pregranulosa cell apoptosis correlates with the inhibition of granulosa cell tumour development.     

7.

Comparison of cell survival models for mixed LET radiation     

Tilly N  Brahme A  Carlsson J  Glimelius B 《International journal of radiation biology》1999,75(2):233-243

PURPOSE: Biophysical models for predicting survival for mixed LET radiations have been investigated by comparisons with experimental results from heavy ion irradiations. The aim was to choose a model for further theoretical studies on the effects of a variable RBE for protons. METHODS AND MATERIALS: Predicted survival curves by the Katz track-structure model, the linear quadratic model, LQ model, by Kellerer and Rossi and the lesion additivity model of Lam were compared to experimental survival curves for V79 cells that were irradiated with a mixture of nitrogen ions with an LET of either 78 or 165 keV/microm and 60Co gamma-rays. RESULTS: Results showed that all three models could predict survival within the uncertainty of the measurements for the different mixed radiation schedules used in this study. CONCLUSION: The choice of model could be made on other grounds, such as the type of model parameters and the availability of biological data for these parameters. Also, the possibility of including dose-rate effects and repair functions should be considered. For the purpose of carrying out theoretical studies on the effects of a variable RBE for protons, the LQ model was preferred.     

8.

The response of a human malignant melanoma cell line to high LET radiation.     

L F Thomson  A R Smith  R M Humphrey 《Radiology》1975,117(1):155-158

The response of a human malignant melanoma cell line in vitro to high linear energy transfer radiation was studied utilizing the neutrons produced by the reaction of 16 and 50 MeV deuterons on beryllium. The relative biological effectiveness (RBE) relative to cobalt-60 gamma radiation was determined under conditions of complete oxygenation. The data indicate that the radioresistance ascribed to malignant melanoma in vivo is not an intrinsic quality of the cell but rather may be mediated by the in vivo environment.     

9.

Irradiated human endothelial progenitor cells induce bystander killing in human non-small cell lung and pancreatic cancer cells     

William T. Turchan  Ronald H. Shapiro  Garrett V. Sevigny  Helen Chin-Sinex  Benjamin Pruden 《International journal of radiation biology》2016,92(8):427-433

Purpose To investigate whether irradiated human endothelial progenitor cells (hEPC) could induce bystander killing in the A549 non-small cell lung cancer (NSCLC) cells and help explain the improved radiation-induced tumor cures observed in A549 tumor xenografts co-injected with hEPC.

Materials and methods We investigated whether co-injection of CBM3 hEPC with A549 NSCLC cells would alter tumor xenograft growth rate or tumor cure after a single dose of 0 or 5?Gy of X-rays. We then utilized dual chamber Transwell dishes, to test whether medium from irradiated CBM3 and CBM4 hEPC would induce bystander cell killing in A549 cells, and as an additional control, in human pancreatic cancer MIA PaCa-2 cells. The CBM3 and CBM4 hEPC were plated into the upper Transwell chamber and the A549 or MIA PaCa-2 cells were plated in the lower Transwell chamber. The top inserts with the CBM3 or CBM4 hEPC cells were subsequently removed, irradiated, and then placed back into the Transwell dish for 3?h to allow for diffusion of any potential bystander factors from the irradiated hEPC in the upper chamber through the permeable membrane to the unirradiated cancer cells in the lower chamber. After the 3?h incubation, the cancer cells were re-plated for clonogenic survival.

Results We found that co-injection of CBM3 hEPC with A549 NSCLC cells significantly increased the tumor growth rate compared to A549 cells alone, but paradoxically also increased A549 tumor cure after a single dose of 5?Gy of X-rays (p?p?p?p?Conclusions These data provide evidence that irradiated hEPC can induce strong bystander killing in A549 and MIA PaCa-2 human cancer cells and that this bystander killing is mediated by the cytokines TNF-α and TGF-β.     

10.

不同LET¹²C⁶⁺照射人肝癌细胞SMMC-7721的存活曲线          下载免费PDF全文

雷苏文  苏旭  王菊芳  李文建 《中华放射医学与防护杂志》2003,23(2):83-85

目的 研究不同传能线密度(LET)的重离子^12C^6 对体外培养的人肝癌细胞SMMC7721存活的影响，以研究人肝癌细胞对不同LET重离子的辐射敏感性。方法 用克隆形成法研究细胞的存活情况。结果 70keV／μm的细胞存活率为10％(Ds=0.1)和1％(Ds=0.01)时的吸收剂量分别为2．94Gy和5．88Gy；30keV／μm的Ds=0.1和Ds=0.01分别为4．00Gy和8．00Gy。结论 70keV／μm比30keV／μm对人肝癌细胞SMMC—7721有更大的细胞杀死效应。     

11.

A composite microdose Adaptive Response (AR) and Bystander Effect (BE) model-application to low LET and high LET AR and BE data   总被引：1，自引：0，他引：1  

Leonard BE 《International journal of radiation biology》2008,84(8):681-701

PURPOSE: It has been suggested that Adaptive Response (AR) may reduce risk of adverse health effects due to ionizing radiation. But very low dose Bystander Effects (BE) may impose dominant deleterious human risks. These conflicting behaviors have stimulated controversy regarding the Linear No-Threshold human risk model. A dose and dose rate-dependent microdose model, to examine AR behavior, was developed in prior work. In the prior work a number of in vitro and in vivo dose response data were examined with the model. Recent new data show AR behavior with some evidence of very low dose BE. The purpose of this work is to supplement the microdose model to encompass the Brenner and colleagues BaD (Bystander and Direct Damage) model and apply this composite model to obtain new knowledge regarding AR and BE and illustrate the use of the model to plan radio-biology experiments. MATERIALS AND METHODS: The biophysical composite AR and BE Microdose Model quantifies the accumulation of hits (Poisson distributed, microdose specific energy depositions) to cell nucleus volumes. This new composite AR and BE model provides predictions of dose response at very low dose BE levels, higher dose AR levels and even higher dose Direct (linear-quadratic) Damage radiation levels. RESULTS: We find good fits of the model to both BE data from the Columbia University microbeam facility and combined AR and BE data for low Linear Energy Transfer (LET) and high LET data. A Bystander Factor of about 27,000 and an AR protection factor of 0.61 are obtained for the low LET in vivo mouse spleen exposures. A Bystander Factor of 317 and an AR protection factor of 0.53 are obtained for high LET radon alpha particles in human lymphocytes. In both cases the AR is activated at most by one or two radiation induced charged particle traversals through the cell nucleus. CONCLUSIONS: The results of the model analysis is consistent with a premise that both Bystander damage and Adaptive Response radioprotection can occur in the same cell type, derived from the same cell species. The model provides an analytical tool to biophysically study the combined effects of BE and AR.     

12.

Biological considerations for treating alternate fields versus all fields daily with high and low LET radiation     

R A Gahbauer  J Horton  F Q Ngo  W Roberts  J Blue 《Strahlentherapie》1985,161(12):771-774

The rationale for treating all fields every day with photons was reviewed. Since the effects of neutron radiation are much less dependent on alterations of fractionation schedules, and since preferential sparing for late effects is not obtained by fractionation of neutron dose, less convincing reasons exist for treating all fields every day with neutrons. Treating one field/day would not alter the physical dose distribution or overall treatment time, yet still maintain biological homogeneity. Preliminary in vitro experiments support this conclusion.     

13.

高-低氧全肺照射对小鼠肺纤维化的影响   总被引：1，自引：2，他引：1       下载免费PDF全文

崔晓利  徐波  王争  沈瑜  殷蔚伯 《中华放射医学与防护杂志》1999,19(2):116-118

目的以小鼠肺组织中ＴＧＦβ１含量变化为指标,观测高低氧（ＨＯ＋ＬＯ）照射对肺晚期损伤的生物学效应。方法雄性Ｃ５７ＢＬ小鼠,１３Ｇｙ全肺一次照射,照射同时分别吸入空气、高氧（９５％Ｏ２＋５％ＣＯ２）或高低氧（１０％Ｏ２＋５％ＣＯ２＋８５％Ｎ２）,照射后不同时间取肺组织ＨＥ染色、Ｍａｓｏｎ染色、Ｖ．Ｇ．染色观察肺纤维化形成。ＲＴＰＣＲ方法测定肺组织内ＴＧＦβ１的表达。结果照射后８个月肺组织局部灶性纤维化形成。高氧组肺纤维化面积大于空气组及ＨＯ＋ＬＯ组,两者相比,差异具有显著性;ＨＯ＋ＬＯ组纤维化面积虽略高于空气组,但差异无显著性。照射后３６小时,ＴＧＦβ１表达下降,照射后２个月,ＴＧＦβ１表达升高,至照射后８个月,略呈下降趋势,但仍高于正常对照。结论低氧的加入降低单纯高氧导致的正常组织损伤,ＨＯ＋ＬＯ照射不增加肺的晚期损伤,ＴＧＦβ１的表达在肺纤维化形成过程中起重要作用     

14.

Effects of ionizing radiations on proliferating cellular systems     

F Bresciani 《Minerva radiologica》1965,10(6):235-244

     

15.

Effects of ionizing radiations on tissue mast cells     

DUTTA-CHOUDHURI R  ROY H 《The International journal of applied radiation and isotopes》1959,4(3-4):268-269

     

16.

稳定低表达CD147的人肺腺癌细胞系的建立及对细胞增殖的影响     

杨绍兴  汤传昊  王思涵  宋三泰  刘晓晴 《军事医学》2012,(12):912-915,928

目的构建CD147慢病毒干涉载体,建立稳定下调CD147表达的人肺腺癌A549细胞系,观察下调CD147表达后人肺腺癌细胞增殖能力的变化。方法将携带不同特异性干涉序列的3个DNA片段分别插入干涉质粒pSicoR中,构建pSicoR-siCD147慢病毒干涉载体(pSicoR-siCD147-1,pSicoR-siCD147-2,pSicoR-siCD147-3)。分别将构建好的载体转染入293FT细胞中,进行慢病毒包装。建立稳定下调CD147表达的细胞系。利用CCK-8法检测细胞增殖能力的变化。结果与结论构建了pSicoR-siCD147慢病毒干涉载体,RT-PCR和实时PCR结果显示pSicoR-siCD147-2的干涉效率最高。建立了稳定下调CD147表达的人肺腺癌A549细胞系(A549-siCD147)。CCK-8法检测发现A549-siCD147细胞的增殖能力显著性下降(P<0.05),下调CD147的表达可以使人肺腺癌细胞的增殖能力受到明显抑制。     

17.

大蒜素对裸鼠体内人肺腺癌细胞SLC-89增殖的影响     

钟燕玲  张永云  李卫真  刘春生 《西南国防医药》2012,22(11):1171-1173

目的观察大蒜素对裸鼠体内人肺腺癌细胞SLC-89增殖的影响。方法采用小鼠肉瘤S180腹水上清悬浮人肺腺癌SLC-89细胞后皮下注射SLC-89细胞给裸鼠的方法制备肿瘤模型,分别在注射细胞的同时和注射细胞后15d,连续45d腹腔注射大蒜素,对照组每天腹腔注射同等体积的生理盐水。然后处死裸鼠,测定肿块的重量,并取肿瘤组织作HE染色。结果采用小鼠肉瘤S180腹水上清悬浮人肺腺癌SLC-89细胞后每只裸鼠皮下注射5×106个SLC-89细胞的方法,可以有效复制人肺腺癌裸鼠模型,成瘤率为100％。注射细胞的同时每只裸鼠连续45d按照15mg／（kg·d）腹腔注射大蒜素溶液,所产生的肿瘤重量明显低于对照组（P〈0．05）;移植细胞后15d,再给每只裸鼠连续45d注射相同剂量的大蒜素,所产生的肿瘤重量与对照组差异不明显（P〉0．05）。与对照组比较,注射细胞的同时就给予大蒜素治疗的裸鼠肿瘤细胞减少或有肿瘤组织坏死。结论按照15mg／（kg·d）的剂量腹腔注射大蒜素,能减缓裸鼠体内人肺腺癌肿块的形成。     

18.

重组人脑利钠肽对高原肺水肿患者肺功能的影响     

彭顺舟  陈业民  刘炜  吴健  和增民 《西南国防医药》2010,20(9):994-996

目的探索重组人脑利钠肽（rhBNP）在治疗高原肺水肿中对患者肺功能的改善情况。方法收集我院自2007年3月～2008年11月的高原肺水肿病例118例,随机分为普通治疗组和重组人脑利钠肽组。两组人院后都给予吸氧、利尿、镇静、扩张支气管、减轻心脏负荷等处理,此外,重组人脑利钠肽组给予重组人脑利钠肽治疗。然后分别于治疗24、48h后,对两组患者进行肺功能检测,比较其治疗效果。结果治疗24、48h后,重组人脑利钠肽组肺活量（VC）、残气量（RV）、肺总量（TLC）较普通治疗组均有明显改善（P〈0．05）;1秒率（FEV1．0％）则无明显变化。结论重组人脑利钠肽可改善高原肺水肿患者的肺功能。     

19.

不同照射方式对结直肠癌CL187细胞的抑制作用和分子机制初探          下载免费PDF全文

王皓  王俊杰  曲昂  李金娜  刘敬佳 《中华放射医学与防护杂志》2012,32(6):574-577

目的 研究单次、分次和125Ⅰ粒子持续低剂量率照射对结直肠癌CL187细胞生物学效应的影响.方法 实验分高剂量率单次照射组(400 cGy/min,单次组)、分次照射组(2 Gy/次/d,400 cGy/min,分次组)和125Ⅰ粒子持续低剂量率照射组(2.77 cGy/h,125Ⅰ组).3组细胞照射0、2、4和8 Gy后,24和48 h进行细胞计数和锥虫蓝染色,比较细胞总数和细胞存活率的差异.利用克隆形成实验比较3组细胞增殖能力的差异.通过流式细胞仪检测细胞凋亡.蛋白免疫印迹法分析PHLPP2、PTEN和Bax蛋白表达的变化.结果 与单次组和分次组相比,125Ⅰ组细胞总数减少(t=34.28和29.48,P＜0.05)、存活细胞比例减少(t=-12.38和-14.61,P＜0.05),细胞克隆形成能力下降,相对生物学效应是1.41.照射后48 h细胞凋亡检测发现125Ⅰ组细胞凋亡比例增加(t=-15.08和-11.99,P＜0.05).蛋白免疫印迹法检测发现125Ⅰ组Bax表达量升高,PHLPP2和PTEN的表达量3组间差异无统计学意义.结论 单次、分次和持续低剂量率照射后细胞PHLPP2蛋白表达水平均升高,但剂量率的高低并不影响其表达水平.不同方式照射后,凋亡相关蛋白Bax的表达水平上升,125Ⅰ组升高更加明显,125Ⅰ持续低剂量粒子照射可能通过影响凋亡相关蛋白Bax的表达水平实现对结直肠癌CL187细胞的杀伤作用.     

20.

Effects of high and low blood lactate concentrations on sweat lactate response     

Green JM  Bishop PA  Muir IH  McLester JR  Heath HE 《International journal of sports medicine》2000,21(8):556-560

Sweat lactate results from eccrine gland metabolism, however, the possible clearance of blood lactate through sweat has not been resolved. On separate days in an environmental chamber (32 +/- 1 C) 12 subjects completed a constant load (CON) (30 min at 40% VO2 max) and an interval cycling trial (INT) (15 one-min intervals at 80% VO2 max, each separated by one min rest) each designed to elicit different blood lactate responses. Each 30 min cycling trial was preceded by 15 min warm-up (30 watts) and followed by 15 min passive rest. Sweat and blood were analyzed for lactate concentration at 15, 25, 35, 45, and 60 min during CON and INT. Total body water loss was used to calculate sweat rate (ml/hr). Blood lactate was significantly greater (p < or = 0.05) at 25, 35, 45, and 60 min during INT compared to CON (approximately 5 mmol/L vs 1.5 mmol/L). Sweat lactate was not significantly different (p>0.05) between trials at any time (approximately 10 mmol/L). Sweat rates (approximately 600ml/hr) and estimated total lactate secretion were not significantly different (CON vs. INT) (p > 0.05). Elevated blood lactate was not associated with changes in sweat lactate concentration. Sweat lactate seems to originate in eccrine glands independent of blood lactate.     

高 LET 和低 LET 辐射体外诱发细胞恶性转化的比较

目的本研究采用体外细胞转化系统，比较观察了高ＬＥＴ（２３８Ｐｕα粒子，５．２５ＭｅＶ）和低ＬＥＴ（Ｘ射线，１８０ｋＶ）辐射体外诱发成年大鼠肺成纤维细胞系（ＷＡＬ－Ｆ１）恶性转化的特点。方法①应用体外细胞转化模型；②观察指标包括转化细胞形态学和生物学特性的改变；③转化细胞在体内的致瘤作用等。结果α粒子和Ｘ射线诱发同一细胞系转化的形态学与生物学特性基本相似，但在生物学效应上二者存在以下的差异：①细胞存活曲线模型，α粒子为单击单靶模型，Ｄ０值为０．１７２Ｇｙ；Ｘ射线为单击多靶模型，Ｄ０值为１．６６Ｇｙ；②对细胞增殖能力、染色体畸变及集落形成率的影响，产生相近的生物效应所需的剂量，α粒子比Ｘ射线约低１０倍；③以在动物体内致瘤性为终点，引发肿瘤的剂量，α粒子对Ｘ射线的ＲＢＥ值为６（３．０／０．５）。结论实验表明，高ＬＥＴ对体外细胞亦具有较高的致瘤效应。     

Differences between biological effects of high LET and low LET radiations in relation to their application in radiotherapy

The application of fast neutrons, negative pions or heavy ions will only provide an advantage for the radiotherapy of cancer if, in comparison with conventional radiation, e.g., X-rays, gamma rays and electrons, better depth-dose and collimation characteristics or specific radiobiological dose-response relationships result in greater local control probabilities for tumours without increased frequencies of severe normal tissue damage. Differences in intrinsic radiosensitivity and the presence of hypoxic cells are considered to be the main factors which can cause values of the relative biological effectiveness (RBE) for responses of tumours to be larger than RBE values for normal tissue tolerance. Clinical studies on lung metastases irradiated with single doses of 15 MeV neutrons indicate that RBE values for tumour growth delay can vary between 1.2 and 4.0, while RBE values for damage to several normal tissues are estimated from data on a few animal tissues to be approximately 2.5.     

Relationship between oocyte apoptosis and ovarian tumours induced by high and low LET radiations in mice

PURPOSE: To investigate the biological effectiveness of neutrons at the energy below 1 MeV on apoptosis and carcinogenesis in the mouse ovary. MATERIALS AND METHODS: Female mice were exposed to 1.0 Gy monoenergetic neutrons (0.317, 0.525 and 1.026 MeV), (252)Cf fission neutron (2.13 MeV) or (137)Cs gamma-rays at 7 days of age. Apoptosis of the oocyte and pregranulosa cells, and ovarian carcinogenesis were compared between the radiations. The efficiency of gamma-rays for granulosa cell tumorigenesis was tested by transplantation of the irradiated ovaries into non-irradiated mice. RESULTS: The cumulative apoptotic index of oocytes was 77.9%, 65.6% and 41.6% for the 0.525 MeV neutron, 2.13 MeV neutron and gamma-rays, respectively. Follicles with apoptotic pregranulosa cells were 53.0%, 18.3% and 22.8% of cumulative index for the three groups. Tubular adenomas developed in the groups of monoenergetic neutrons (26.1%) and gamma-ray (35.5%), whereas granulosa cell tumours developed only in the gamma-ray groups (3.2% for 1.0 Gy and 15.6% for 3.0 Gy). Partial-body irradiation with 3 Gy gamma-rays to the ovaries induced granulosa cell tumours with an incidence of 27.3%. CONCLUSION: Effectiveness of neutrons to cause apoptosis was higher for 0.525 MeV than for 2.13 MeV. The pregranulosa cell apoptosis occurred in an oocyte-prone manner. The higher effectiveness of neutrons than gamma-rays to induce oocyte and pregranulosa cell apoptosis correlates with the inhibition of granulosa cell tumour development.     

Radiation response of primary human skin fibroblasts and their bystander cells after exposure to counted particles at low and high LET

PURPOSE: To investigate the dependence of bystander effects on linear energy transfer (LET) in the low dose region. MATERIALS AND METHODS: The single-ion microbeam of the Physikalisch-Technische Bundesanstalt (PTB) was used to irradiate confluent primary human skin fibroblasts. Cells plated on a special irradiation dish were targeted with 10 MeV protons (LET 4.7 keV/microm) and 4.5 MeV a-particles (LET 100 keV/microm). During exposure, the cells were confluent allowing signal transfers through both gap junctions and diffusion. RESULTS: For 10 MeV protons the clonogenic capability was significantly higher after exposure to 70 protons (0.31 Gy) compared with unirradiated cells. For higher doses the survival curve was exponential. Exposure of only 10% of all nuclei resulted in a similar radiation response in the low dose region. For higher doses up to 2.2 Gy no cell killing was observed. For 4.5 MeV alpha-particles an exponential survival curve was obtained. Irradiation of only 10% of all cell nuclei resulted in an survival curve as had been expected in the absence of any bystander effect. CONCLUSION: The type and extent of bystander effects turned out to be dependent on the particles' LET and are likely to depend also on the cell line used and the techniques applied.     

Relationship between oocyte apoptosis and ovarian tumours induced by high and low LET radiations in mice

Purpose : To investigate the biological effectiveness of neutrons at the energy below 1 MeV on apoptosis and carcinogenesis in the mouse ovary. Materials and methods : Female mice were exposed to 1.0 Gy monoenergetic neutrons (0.317, 0.525 and 1.026 MeV), 252 Cf fission neutron (2.13 MeV) or 137 Cs γ-rays at 7 days of age. Apoptosis of the oocyte and pregranulosa cells, and ovarian carcinogenesis were compared between the radiations. The efficiency of γ-rays for granulosa cell tumorigenesis was tested by transplantation of the irradiated ovaries into non-irradiated mice. Results : The cumulative apoptotic index of oocytes was 77.9%, 65.6% and 41.6% for the 0.525 MeV neutron, 2.13 MeV neutron and γ-rays, respectively. Follicles with apoptotic pregranulosa cells were 53.0%, 18.3% and 22.8% of cumulative index for the three groups. Tubular adenomas developed in the groups of monoenergetic neutrons (26.1%) and γ-ray (35.5%), whereas granulosa cell tumours developed only in the γ-ray groups (3.2% for 1.0 Gy and 15.6% for 3.0 Gy). Partial-body irradiation with 3 Gy γ-rays to the ovaries induced granulosa cell tumours with an incidence of 27.3%. Conclusion : Effectiveness of neutrons to cause apoptosis was higher for 0.525 MeV than for 2.13 MeV. The pregranulosa cell apoptosis occurred in an oocyte-prone manner. The higher effectiveness of neutrons than γ-rays to induce oocyte and pregranulosa cell apoptosis correlates with the inhibition of granulosa cell tumour development.     

Comparison of cell survival models for mixed LET radiation

PURPOSE: Biophysical models for predicting survival for mixed LET radiations have been investigated by comparisons with experimental results from heavy ion irradiations. The aim was to choose a model for further theoretical studies on the effects of a variable RBE for protons. METHODS AND MATERIALS: Predicted survival curves by the Katz track-structure model, the linear quadratic model, LQ model, by Kellerer and Rossi and the lesion additivity model of Lam were compared to experimental survival curves for V79 cells that were irradiated with a mixture of nitrogen ions with an LET of either 78 or 165 keV/microm and 60Co gamma-rays. RESULTS: Results showed that all three models could predict survival within the uncertainty of the measurements for the different mixed radiation schedules used in this study. CONCLUSION: The choice of model could be made on other grounds, such as the type of model parameters and the availability of biological data for these parameters. Also, the possibility of including dose-rate effects and repair functions should be considered. For the purpose of carrying out theoretical studies on the effects of a variable RBE for protons, the LQ model was preferred.     

The response of a human malignant melanoma cell line to high LET radiation.

The response of a human malignant melanoma cell line in vitro to high linear energy transfer radiation was studied utilizing the neutrons produced by the reaction of 16 and 50 MeV deuterons on beryllium. The relative biological effectiveness (RBE) relative to cobalt-60 gamma radiation was determined under conditions of complete oxygenation. The data indicate that the radioresistance ascribed to malignant melanoma in vivo is not an intrinsic quality of the cell but rather may be mediated by the in vivo environment.     

Irradiated human endothelial progenitor cells induce bystander killing in human non-small cell lung and pancreatic cancer cells

Purpose To investigate whether irradiated human endothelial progenitor cells (hEPC) could induce bystander killing in the A549 non-small cell lung cancer (NSCLC) cells and help explain the improved radiation-induced tumor cures observed in A549 tumor xenografts co-injected with hEPC.

Materials and methods We investigated whether co-injection of CBM3 hEPC with A549 NSCLC cells would alter tumor xenograft growth rate or tumor cure after a single dose of 0 or 5?Gy of X-rays. We then utilized dual chamber Transwell dishes, to test whether medium from irradiated CBM3 and CBM4 hEPC would induce bystander cell killing in A549 cells, and as an additional control, in human pancreatic cancer MIA PaCa-2 cells. The CBM3 and CBM4 hEPC were plated into the upper Transwell chamber and the A549 or MIA PaCa-2 cells were plated in the lower Transwell chamber. The top inserts with the CBM3 or CBM4 hEPC cells were subsequently removed, irradiated, and then placed back into the Transwell dish for 3?h to allow for diffusion of any potential bystander factors from the irradiated hEPC in the upper chamber through the permeable membrane to the unirradiated cancer cells in the lower chamber. After the 3?h incubation, the cancer cells were re-plated for clonogenic survival.

Results We found that co-injection of CBM3 hEPC with A549 NSCLC cells significantly increased the tumor growth rate compared to A549 cells alone, but paradoxically also increased A549 tumor cure after a single dose of 5?Gy of X-rays (p?p?p?p?Conclusions These data provide evidence that irradiated hEPC can induce strong bystander killing in A549 and MIA PaCa-2 human cancer cells and that this bystander killing is mediated by the cytokines TNF-α and TGF-β.     

不同LET12C6+照射人肝癌细胞SMMC-7721的存活曲线

目的 研究不同传能线密度(LET)的重离子^12C^6 对体外培养的人肝癌细胞SMMC7721存活的影响，以研究人肝癌细胞对不同LET重离子的辐射敏感性。方法 用克隆形成法研究细胞的存活情况。结果 70keV／μm的细胞存活率为10％(Ds=0.1)和1％(Ds=0.01)时的吸收剂量分别为2．94Gy和5．88Gy；30keV／μm的Ds=0.1和Ds=0.01分别为4．00Gy和8．00Gy。结论 70keV／μm比30keV／μm对人肝癌细胞SMMC—7721有更大的细胞杀死效应。     

A composite microdose Adaptive Response (AR) and Bystander Effect (BE) model-application to low LET and high LET AR and BE data

PURPOSE: It has been suggested that Adaptive Response (AR) may reduce risk of adverse health effects due to ionizing radiation. But very low dose Bystander Effects (BE) may impose dominant deleterious human risks. These conflicting behaviors have stimulated controversy regarding the Linear No-Threshold human risk model. A dose and dose rate-dependent microdose model, to examine AR behavior, was developed in prior work. In the prior work a number of in vitro and in vivo dose response data were examined with the model. Recent new data show AR behavior with some evidence of very low dose BE. The purpose of this work is to supplement the microdose model to encompass the Brenner and colleagues BaD (Bystander and Direct Damage) model and apply this composite model to obtain new knowledge regarding AR and BE and illustrate the use of the model to plan radio-biology experiments. MATERIALS AND METHODS: The biophysical composite AR and BE Microdose Model quantifies the accumulation of hits (Poisson distributed, microdose specific energy depositions) to cell nucleus volumes. This new composite AR and BE model provides predictions of dose response at very low dose BE levels, higher dose AR levels and even higher dose Direct (linear-quadratic) Damage radiation levels. RESULTS: We find good fits of the model to both BE data from the Columbia University microbeam facility and combined AR and BE data for low Linear Energy Transfer (LET) and high LET data. A Bystander Factor of about 27,000 and an AR protection factor of 0.61 are obtained for the low LET in vivo mouse spleen exposures. A Bystander Factor of 317 and an AR protection factor of 0.53 are obtained for high LET radon alpha particles in human lymphocytes. In both cases the AR is activated at most by one or two radiation induced charged particle traversals through the cell nucleus. CONCLUSIONS: The results of the model analysis is consistent with a premise that both Bystander damage and Adaptive Response radioprotection can occur in the same cell type, derived from the same cell species. The model provides an analytical tool to biophysically study the combined effects of BE and AR.     

Biological considerations for treating alternate fields versus all fields daily with high and low LET radiation

The rationale for treating all fields every day with photons was reviewed. Since the effects of neutron radiation are much less dependent on alterations of fractionation schedules, and since preferential sparing for late effects is not obtained by fractionation of neutron dose, less convincing reasons exist for treating all fields every day with neutrons. Treating one field/day would not alter the physical dose distribution or overall treatment time, yet still maintain biological homogeneity. Preliminary in vitro experiments support this conclusion.     

高-低氧全肺照射对小鼠肺纤维化的影响

目的以小鼠肺组织中ＴＧＦβ１含量变化为指标,观测高低氧（ＨＯ＋ＬＯ）照射对肺晚期损伤的生物学效应。方法雄性Ｃ５７ＢＬ小鼠,１３Ｇｙ全肺一次照射,照射同时分别吸入空气、高氧（９５％Ｏ２＋５％ＣＯ２）或高低氧（１０％Ｏ２＋５％ＣＯ２＋８５％Ｎ２）,照射后不同时间取肺组织ＨＥ染色、Ｍａｓｏｎ染色、Ｖ．Ｇ．染色观察肺纤维化形成。ＲＴＰＣＲ方法测定肺组织内ＴＧＦβ１的表达。结果照射后８个月肺组织局部灶性纤维化形成。高氧组肺纤维化面积大于空气组及ＨＯ＋ＬＯ组,两者相比,差异具有显著性;ＨＯ＋ＬＯ组纤维化面积虽略高于空气组,但差异无显著性。照射后３６小时,ＴＧＦβ１表达下降,照射后２个月,ＴＧＦβ１表达升高,至照射后８个月,略呈下降趋势,但仍高于正常对照。结论低氧的加入降低单纯高氧导致的正常组织损伤,ＨＯ＋ＬＯ照射不增加肺的晚期损伤,ＴＧＦβ１的表达在肺纤维化形成过程中起重要作用     

稳定低表达CD147的人肺腺癌细胞系的建立及对细胞增殖的影响

目的构建CD147慢病毒干涉载体,建立稳定下调CD147表达的人肺腺癌A549细胞系,观察下调CD147表达后人肺腺癌细胞增殖能力的变化。方法将携带不同特异性干涉序列的3个DNA片段分别插入干涉质粒pSicoR中,构建pSicoR-siCD147慢病毒干涉载体(pSicoR-siCD147-1,pSicoR-siCD147-2,pSicoR-siCD147-3)。分别将构建好的载体转染入293FT细胞中,进行慢病毒包装。建立稳定下调CD147表达的细胞系。利用CCK-8法检测细胞增殖能力的变化。结果与结论构建了pSicoR-siCD147慢病毒干涉载体,RT-PCR和实时PCR结果显示pSicoR-siCD147-2的干涉效率最高。建立了稳定下调CD147表达的人肺腺癌A549细胞系(A549-siCD147)。CCK-8法检测发现A549-siCD147细胞的增殖能力显著性下降(P<0.05),下调CD147的表达可以使人肺腺癌细胞的增殖能力受到明显抑制。     

大蒜素对裸鼠体内人肺腺癌细胞SLC-89增殖的影响

目的观察大蒜素对裸鼠体内人肺腺癌细胞SLC-89增殖的影响。方法采用小鼠肉瘤S180腹水上清悬浮人肺腺癌SLC-89细胞后皮下注射SLC-89细胞给裸鼠的方法制备肿瘤模型,分别在注射细胞的同时和注射细胞后15d,连续45d腹腔注射大蒜素,对照组每天腹腔注射同等体积的生理盐水。然后处死裸鼠,测定肿块的重量,并取肿瘤组织作HE染色。结果采用小鼠肉瘤S180腹水上清悬浮人肺腺癌SLC-89细胞后每只裸鼠皮下注射5×106个SLC-89细胞的方法,可以有效复制人肺腺癌裸鼠模型,成瘤率为100％。注射细胞的同时每只裸鼠连续45d按照15mg／（kg·d）腹腔注射大蒜素溶液,所产生的肿瘤重量明显低于对照组（P〈0．05）;移植细胞后15d,再给每只裸鼠连续45d注射相同剂量的大蒜素,所产生的肿瘤重量与对照组差异不明显（P〉0．05）。与对照组比较,注射细胞的同时就给予大蒜素治疗的裸鼠肿瘤细胞减少或有肿瘤组织坏死。结论按照15mg／（kg·d）的剂量腹腔注射大蒜素,能减缓裸鼠体内人肺腺癌肿块的形成。     

重组人脑利钠肽对高原肺水肿患者肺功能的影响

目的探索重组人脑利钠肽（rhBNP）在治疗高原肺水肿中对患者肺功能的改善情况。方法收集我院自2007年3月～2008年11月的高原肺水肿病例118例,随机分为普通治疗组和重组人脑利钠肽组。两组人院后都给予吸氧、利尿、镇静、扩张支气管、减轻心脏负荷等处理,此外,重组人脑利钠肽组给予重组人脑利钠肽治疗。然后分别于治疗24、48h后,对两组患者进行肺功能检测,比较其治疗效果。结果治疗24、48h后,重组人脑利钠肽组肺活量（VC）、残气量（RV）、肺总量（TLC）较普通治疗组均有明显改善（P〈0．05）;1秒率（FEV1．0％）则无明显变化。结论重组人脑利钠肽可改善高原肺水肿患者的肺功能。     

不同照射方式对结直肠癌CL187细胞的抑制作用和分子机制初探

目的 研究单次、分次和125Ⅰ粒子持续低剂量率照射对结直肠癌CL187细胞生物学效应的影响.方法 实验分高剂量率单次照射组(400 cGy/min,单次组)、分次照射组(2 Gy/次/d,400 cGy/min,分次组)和125Ⅰ粒子持续低剂量率照射组(2.77 cGy/h,125Ⅰ组).3组细胞照射0、2、4和8 Gy后,24和48 h进行细胞计数和锥虫蓝染色,比较细胞总数和细胞存活率的差异.利用克隆形成实验比较3组细胞增殖能力的差异.通过流式细胞仪检测细胞凋亡.蛋白免疫印迹法分析PHLPP2、PTEN和Bax蛋白表达的变化.结果 与单次组和分次组相比,125Ⅰ组细胞总数减少(t=34.28和29.48,P＜0.05)、存活细胞比例减少(t=-12.38和-14.61,P＜0.05),细胞克隆形成能力下降,相对生物学效应是1.41.照射后48 h细胞凋亡检测发现125Ⅰ组细胞凋亡比例增加(t=-15.08和-11.99,P＜0.05).蛋白免疫印迹法检测发现125Ⅰ组Bax表达量升高,PHLPP2和PTEN的表达量3组间差异无统计学意义.结论 单次、分次和持续低剂量率照射后细胞PHLPP2蛋白表达水平均升高,但剂量率的高低并不影响其表达水平.不同方式照射后,凋亡相关蛋白Bax的表达水平上升,125Ⅰ组升高更加明显,125Ⅰ持续低剂量粒子照射可能通过影响凋亡相关蛋白Bax的表达水平实现对结直肠癌CL187细胞的杀伤作用.     

Effects of high and low blood lactate concentrations on sweat lactate response

Sweat lactate results from eccrine gland metabolism, however, the possible clearance of blood lactate through sweat has not been resolved. On separate days in an environmental chamber (32 +/- 1 C) 12 subjects completed a constant load (CON) (30 min at 40% VO2 max) and an interval cycling trial (INT) (15 one-min intervals at 80% VO2 max, each separated by one min rest) each designed to elicit different blood lactate responses. Each 30 min cycling trial was preceded by 15 min warm-up (30 watts) and followed by 15 min passive rest. Sweat and blood were analyzed for lactate concentration at 15, 25, 35, 45, and 60 min during CON and INT. Total body water loss was used to calculate sweat rate (ml/hr). Blood lactate was significantly greater (p < or = 0.05) at 25, 35, 45, and 60 min during INT compared to CON (approximately 5 mmol/L vs 1.5 mmol/L). Sweat lactate was not significantly different (p>0.05) between trials at any time (approximately 10 mmol/L). Sweat rates (approximately 600ml/hr) and estimated total lactate secretion were not significantly different (CON vs. INT) (p > 0.05). Elevated blood lactate was not associated with changes in sweat lactate concentration. Sweat lactate seems to originate in eccrine glands independent of blood lactate.