The Calculation of Radiation Dose from Distributed Sources of Tritium

Summary

Formulae derived by Rossi and Ellis (1950) for the calculation of radiation dose from distributed sources of beta-emitters have been made applicable to the case of tritium by a consideration of the appropriate value for the effective absorption coefficient employed in these expressions. An example is given of their application to the calculation of dose to a cell from tritium incorporated in the nucleus.     

Interaction between the biological effects of high- and low-LET radiation dose components in a mixed field exposure

Abstract

Purpose: The relative biological effectiveness of two epithermal neutron sources, a reactor based source at Studsvik, Sweden, and a proton accelerator-based source in Birmingham, UK, was studied in relation to the proportional absorbed dose distribution as a function of neutron energy. Evidence for any interactions between the effects of biological damage induced by high- and low-linear energy transfer (LET) dose components, in this ‘mixed field’ irradiation, was also examined

Materials and methods: Clonogenic survival in Chinese Hamster-derived V79 cells was used to assess biological effectiveness in this study. Cells were irradiated in suspension at 4°C at depths of 20, 35, 50 and 65 mm in a water phantom. This prevented the repair of sublethal damage, predominantly that produced by both incident and induced γ-rays in the field, over the variable periods of exposure required to irradiate cells with the same total absorbed dose. Cell survival, as a function of the absorbed radiation dose and depth in the phantom, was compared with Monte Carlo N-Particle (MCNP) calculations of the proportional absorbed dose distribution as a function of neutron energy for the two sources.

Results: In terms of the dose-related reduction in clonogenic cell survival, the epithermal neutron source at Studsvik was more biologically effective than the Birmingham source at all depths considered in the phantom. Although the contribution from the high-LET dose component was greater for the Studsvik source at 20 mm depth in the phantom, at greater depths the dose contribution from the high-LET dose component at Studsvik overlap with those for the Birmingham source. However, the most striking difference is in the fast neutron component to the dose of the two sources, neutron energies > 1 MeV were only associated with the Studsvik source. The relative biological effectiveness (RBE) of both sources declined slightly with depth in the phantom, as the total high-LET dose component declined. The maximum source RBE for Studsvik was 2.70 ± 0.50 at 20 mm; reduced to 2.10 ± 0.35 at depths of 50 and 65 mm. The corresponding values for Birmingham were 1.68 ± 0.25 and 1.31 ± 0.19, all values relate only to the surviving fraction of V79 cells at 37%, since RBE values are only applicable to the selected endpoint. Based on a dose reduction factor (DRF) of 1.0 for the total low-LET component to the absorbed dose, the RBE values for the high-LET dose component (fast neutrons and induced protons from the nitrogen capture reaction) was 14.5 and 7.05 for the Studsvik and Birmingham neutron sources, respectively. This is well outside the range of RBE historically reported values for V79 cells for the same level of cell survival for fast neutrons. The calculation of RBE values, based on the proportional absorbed dose distribution as a function of neutron energy, from historical data, and using a RBE of 1.8 for the dose from the nitrogen capture reaction, suggests RBE values for the total high-LET dose component of 3.1–2.8 and 2.5–2.0 for Studsvik and Birmingham, respectively, values again declining with depth in the phantom.

Conclusions: The overall biological effectiveness of the mixed field irradiation from an epithermal neutron sources depends on the composition and quality of the different dose components. The experimentally derived RBE values for the total high-LET dose components in these ‘mixed field’ irradiations are well in excess of historical data for fast neutrons. The difference between the historically expected and the observed RBE values is attributed to the interactions between the damage produced by high- and low-LET radiation.     

A novel vertebrate system for the examination and direct comparison of the relative biological effectiveness for different radiation qualities and sources

Purpose: The recent rapid increase of hadron therapy applications requires the development of high performance, reliable in vivo models for preclinical research on the biological effects of high linear energy transfer (LET) particle radiation.

Aim: The aim of this paper was to test the relative biological effectiveness (RBE) of the zebrafish embryo system at two neutron facilities.

Material and Methods: Series of viable zebrafish embryos at 24-hour post-fertilization (hpf) were exposed to single fraction, whole-body, photon and neutron (reactor fission neutrons (<En?=?1?MeV>) and (p (18?MeV)+Be, <En>?=?3.5?MeV) fast neutron) irradiation. The survival and morphologic abnormalities of each embryo were assessed at 24-hour intervals from the point of fertilization up to 192 hpf and then compared to conventional 6?MV photon beam irradiation results.

Results: The higher energy of the fast neutron beams represents lower RBE (ref. source LINAC 6?MV photon). The lethality rate in the zebrafish embryo model was 10 times higher for 1?MeV fission neutrons and 2.5 times greater for p (18?MeV)+Be cyclotron generated fast neutron beam when compared to photon irradiation results. Dose-dependent organ perturbations (shortening of the body length, spine curvature, microcephaly, micro-ophthalmia, pericardial edema and inhibition of yolk sac resorption) and microscopic (marked cellular changes in eyes, brain, liver, muscle and the gastrointestinal system) changes scale together with the dose response.

Conclusion: The zebrafish embryo system is a powerful and versatile model for assessing the effect of ionizing radiation with different LET values on viability, organ and tissue development.     

Radiobiological evaluation and correlation with the local effect model (LEM) of carbon ion radiation therapy and temozolomide in glioblastoma cell lines

Purpose:?To investigate the cytotoxic effect of high linear-energy transfer (LET) carbon irradiation on glioblastoma cells lines in combination with temozolomide (TMZ).

Methods and materials:?The cell lines U87-MG expressing wild-type p53 and LN229 expressing both mutant and wild-type p53 were irradiated with monoenergetic carbon ion beams (LET 172 keV/μm) or an extended Bragg peak (LET 103 keV/μm) after treatment with 10 μM or 20 μM TMZ. Cytotoxicity was measured by a clonogenic survival assay, and cell growth as well as cell cycle progression, were examined.

Results:?The p53 mutant was more sensitive to X-ray irradiation than the p53 wild type cell line, which was also expressed in a shorter G2 block. High LET carbon ions show an increased biological effectiveness in both cell lines, which is consistent with the predictive calculations by the Local Effect Model (LEM) introduced by Scholz et al. The cell line LN229 was more sensitive to TMZ treatment than the U87MG cell line expressing wild-type p53 only. The combination of TMZ and irradiation showed an additive effect in both cell lines.

Conclusion:?High LET carbon ion irradiation is significantly more effective for glioblastoma cell lines compared to photon irradiation. An additional treatment with TMZ may offer a great chance especially for several tumor types.     

Dose-response and relative biological effectiveness of fast neutrons: Induction of apoptosis and inhibition of neurogenesis in the hippocampus of adult mice

Purpose:?Our study compared the effects of high linear energy transfer (LET) fast neutrons on the induction of apoptosis and reduction of neurogenesis in the hippocampus of adult ICR mice with those of low-LET ⁶⁰Co γ-rays, to evaluate the relative biological effectiveness (RBE) of fast neutrons in the adult hippocampal dentate gyrus (DG).

Materials and Methods:?The mice were exposed to 35 MeV fast neutrons or ⁶⁰Co γ-rays. We evaluated acutely the incidence of apoptosis and expression of Ki-67 (a protein marker for cell proliferation originally defined by the monoclonal antibody Kiel-67) and doublecortin (DCX: an immature progenitor neuron marker) in the hippocampus after a single whole-body irradiation.

Results:?The number of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labelling (TUNEL)-positive apoptotic nuclei in the DG increased and both Ki-67- and DCX-positive cells declined in a dose-dependent pattern, with fast neutrons or γ-rays. In the hippocampus, which showed an apoptosis frequency between 2 and 8 per DG, the RBE of fast neutrons was approximately 1.9. Additionally, the inhibitory effects of fast neutrons on the expression frequencies of Ki-67 (4–8) and DCX (8–32) were approximately 3.2 and 2.5 times, respectively, the effects of γ-rays at the same dose.

Conclusions:?Increased apoptotic cell death and decreased neurogenesis in the hippocampal DG were seen in a dose-dependent pattern after exposure to fast neutrons and γ-rays. In addition, the different rate of hippocampal neurogenesis between different radiation qualities may be an index of RBE.     

A Comparison of the Response to Injected Radioactive Phosphorus and to X-rays in the Haematopoietic Tissue of Rats

The radiation response of haematopoietic tissue in rats following the administration of ³²P is compared with the response to acute whole-body x-irradiation in terms of the radiation dose to different tissues, using thick-section autoradiography for measuring the radiation dose to the bone-marrow in the animals treated with ³²P. Changes in the peripheral blood picture and results of ⁵⁹Fe tracer studies in splenectomized and intact rats are presented.

In spite of considerable differences in the conditions of irradiation, a number of similarities in the response of haematopoietic tissue are obtained with these two methods of irradiation. It is suggested that there is little or no dose-rate effect over the range ～ 30 r/min to ～ 0·2 rads/min for this tissue. A considerably earlier recovery of erythropoiesis in the spleen after ³²P than after x-irradiation is demonstrated.     

低浓度乙醇诱导与紫外线照射对HepG2细胞周期及p53/p21蛋白表达的影响

目的观察低浓度乙醇诱导与紫外线照射导致HepG2肝癌细胞损伤的分子路径。方法选用HepG2肝癌细胞株，分别给予低浓度乙醇诱导与紫外线照射处理，观察两种损伤因素作用后细胞周期分布的差异，细胞中p53蛋白和p21蛋白表达的改变，分析蛋白表达与细胞周期改变的关系。结果紫外线照射后细胞中p53、p21蛋白表达均明显增强，出现G0～G1／G2～M期阻滞；低浓度乙醇诱导后主要出现G2～M期阻滞与p21蛋白表达的增强，p53蛋白表达改变不明显；两种损伤因素均能导致细胞凋亡率的增加。结论低浓度乙醇诱导与紫外线照射通过激活细胞内不同的分子事件，导致细胞周期与细胞凋亡的改变。     

放射损伤细胞中高尔基体弥散现象及香兰素衍生物的防护作用

目的：通过观察辐射对高尔基体形态的影响,确定香兰素衍生物VND3207对受照细胞高尔基体的防护作用。方法采用免疫荧光技术检测放射损伤细胞中高尔基体弥散现象并统计弥散面积,检测细胞周期变化,分析细胞存活率,同时对高尔基体蛋白的表达水平进行检测。结果免疫荧光检测结果显示,照射后高尔基体的弥散面积增加,具有一定的剂量效应和时间效应;VND3207能减轻γ射线对高尔基体的损伤,其表现为与未加药组相比,在抑制不同剂量照射后可使高尔基体弥散面积增加;细胞周期测定结果显示,4 Gy γ线照射后G2／M期阻滞峰值约出现在12 h后;免疫印迹结果显示DNA损伤引起的G2／M期阻滞也在12 h后解除;而高尔基体弥散在细胞周期阻滞解除后12和24 h仍然存在;平板克隆结果显示,VND3207促进了受照细胞的存活。结论放射损伤能引起剂量依赖性高尔基体弥散效应,且这种弥散与DNA损伤诱导的周期阻滞无关,VND3207对放射损伤引起的高尔基体弥散有一定的抑制作用,可能与受照细胞受到保护有关。     

葛根水提取物对小鼠红细胞膜脂流动性和血常规的影响

目的研究葛根水提取物对小鼠红细胞膜脂流动性和血常规的影响。方法小鼠给予葛根水提取物(0.01、0.1、1g·ml-1)3个剂量,并设阴性、阳性对照组,连续给药20d,于停药次日眼球取血,用DPH荧光探针法测定红细胞膜脂流动性;用血细胞分析仪进行血常规检测。结果葛根水提取物0.1、1g·ml-1剂量组、阳性对照组与阴性对照组相比,红细胞膜脂流动性有显著增高(P<0.05),并显著降低微黏度(P<0.05)。血常规检测中葛根水提取物3个剂量组,阳性对照组与阴性对照组相比WBC、MCV、PLT有轻微下降的趋势,无显著影响(P>0.05)。结论葛根能明显升高红细胞膜脂流动性,降低微黏度,改善微循环,具有良好的活血化瘀作用。使用中注意其不良反应,定期检查血常规。     

体外培养人胎肝细胞与永生化L-02肝细胞的生物学性状比较

目的 对比体外培养的人胎肝细胞与L-02肝细胞形态学及增殖分化特征的异同，初步评价其用于移植的可行性，探讨介入性肝细胞移植术的理想供体来源。方法 分离培养14～24周的引产胎儿肝细胞，放射免疫法测定上清液中甲胎蛋白(AFP)与白蛋白(ALB)含量，免疫细胞化学法检测细胞角蛋白19(CK—19)的表达。同法检测传代培养L-02肝细胞的蛋白表达。结果人胎肝细胞分离活率达95％，在体外存活最长达3周，可同时检测到AFP、ALB及CK—19表达，其中ALB分泌峰值42．06μg／ml；L-02肝细胞增殖迅速，AFP与CK-19表达阴性，ALB表达在10μg／ml水平，部分细胞多次传代后发生形态变异，ALB表达缺失。结论人胎肝细胞具有潜在的双向分化能力，是肝细胞移植较为合适的供体来源；L-02肝细胞不适用于移植。     

胃腺癌CDC25A表达及青蒿琥酯干预的实验研究

目的 初步探讨细胞分裂周期素25A(CDC25A)与胃腺癌发生、发展的关系,以及青蒿琥酯对其的干预作用.方法 利用流式细胞术检测胃腺癌组织中CDC25A蛋白表达水平.细胞水平实验分为4组:对照组及30、60、120μmol/L青蒿琥酯组,即以不同浓度(30、60、120μmol/L)青蒿琥酯(Art)干预胃腺癌SGC-7901细胞24h,并以生理盐水代替药物作为对照组,流式细胞术检测细胞凋亡、细胞周期及CDC25A蛋白表达水平.结果 胃腺癌组织中CDC25A蛋白表达水平(419.69±21.91)明显高于正常胃组织中的表达水平(316.11±24.23,P<0.01).30、60、120μmol/L青蒿琥酯组细胞凋亡率(分别为5.48%±0.67%、12.55%±1.17%、23.43%±2.18%)明显高于对照组(0.87%±0.14%,P<0.05),且具有Art剂量依赖性.30、60、120μmol/L青蒿琥酯组细胞增殖指数(分别为39.18%±0.53%、35.71%±0.99%、31.73%±1.02%)明显低于对照组(44.12%±2.51%,P<0.01);30、60、120μmol/L青蒿琥酯组细胞中CDC25A蛋白表达水平(分别为414.80±4.06、397.86±3.61、345.68±7.11)明显低于对照组(433.99±1.56,P<0.01).结论 CDC25A在胃腺癌组织中的高表达可能参与了胃腺癌的发生、发展,Art具有抑制胃腺癌SGC-7901的细胞生长作用,且可以下调细胞CDC25A的蛋白表达水平.     

MEBO与SD-Ag霜对比治疗烧伤70例临床体会

目的；比较MEBO（湿润烧伤膏）与SD－Ag（磺胺密啶银）霜治疗不同烧伤创面的疗效。方法：随机选择70例烧伤病例，35例烧伤创面采用MEBO治疗（治疗组）；35例采用SD－Ag霜治疗（对照组），观察两组不同深度烧伤创面的愈合时间、感染发生率及瘢痕发生率。结果：治疗组创面愈合时间、感染率及瘢痕出现率均明显低于对照组。结论：在烧伤治疗中，MEBO作用明显优于SD－Ag霜。     

MEBO与医用AV创面霜治疗残余创面的临床观察

目的比较MEBO和医用AV创面霜对烧伤残余创面的疗效。方法随机选择61例烧伤后残余创面,31例采用湿润烧伤膏(MEBO)治疗(治疗组),30例采用医用AV创面霜治疗(对照组),观察两组的临床治疗效果。结果治疗组一周后细菌检出率由61.3％下降为12.9％,创面平均愈合天数为14.5±2.4;较对照组明显缩短,愈合后的创面光滑平整,无瘢痕形成。结论残余创面采用MEBO治疗是一种最佳治疗途径。     

S100A4在癌细胞中的作用及其在寻找新治疗靶标中的应用

S100A4是由101个氨基酸组成的多肽,属于Ca2＋结合蛋白超家族中的一员,通过与Ca2＋结合在肿瘤发生发展中发挥重要作用。它在多种肿瘤细胞中都呈高表达,在肿瘤的生长、侵袭和迁移过程中发挥重要作用,是一个与细胞周期、增殖、凋亡、侵袭转移密切相关的蛋白。现就S100A4的结构、功能及其作为癌症治疗新靶标的应用做一综述。     

MEBO与SD-Ag对比治疗会阴部深Ⅱ度烧伤60例临床体会

目的：比较湿润烧伤膏和磺胺嘧啶银在治疗会阴部深Ⅱ度烧伤中的疗效。方法：随机选择６０全有部深Ⅱ度烧伤伤,３０例采用湿润烧伤膏治疗（Ｍ组）,３０例采用１％的磺胺嘧啶银治疗效果。结果：Ｍ组疼痛发生率,疤痕出现率,感染发生率以及手术例数,创面愈合时间均明显低Ｓ组,（Ｐ〈０．００５）,有显性差异。结论：在治疗会阴部深Ⅱ度烧伤时湿润烧成于磺胺嘧啶银。     

MEBT/MEBO与包扎疗法在治疗烧伤中的临床比较

目的：观察MEBT／MEBO与传统包扎疗法治疗烧伤的疗效。方法：在300例烧伤病人中，238例采用MEBT／MEBO技术，68例采用传统包扎疗法，比较两种方法用药后病人的疼痛感觉，活动情况，愈合时间和有无后遗症等情况。结果：MEBT／MEBO技术比传统包扎疗法在烧伤治疗中全面的优势。结论：MEBT／MEBO技术明显优于传统包扎疗法。     

经侧脑室后角灌洗与侧脑室前角穿刺引流对重症脑室出血疗效的比较研究

目的　探讨治疗脑室出血的有效治疗方法。方法　采用侧脑室后角穿刺引流、大量生理盐水灌洗治疗脑室出血 3 6例 ,并与同期单纯侧脑室前角穿刺引流治疗脑室出血 3 3例进行比较。结果　观察组 3 6例 ,显效 2 4例 ,有效 6例 ,无效 6例 ,死亡 6例 ,死亡率 16 7% ,有效率 83 .3 % ,对照组 3 3例 ,显效 18例 ,有效 1例 ,无效 6例 ,死亡 8例 ,死亡率 2 4.2 % ,有效率 5 7.6%。两组比较具有显著差异 ,P <0 .0 5。结论　侧脑室后角穿刺、灌洗治疗脑室出血简便易行、有效。     

奈替米星与阿米卡星治疗下呼吸道感染的临床疗效比较

目的以阿米卡星为对照评价奈替米星治疗下呼吸道感染的临床有效性及安全性。方法共入选病例132例,可评价疗效者102例,其中试验组（奈替米星）与对照组（阿米卡星）分别为52例与50例。安全性评价入选病例113例,两组分别为56例与57例。给药方法试验组每次200mg,每日1次,对照组每次200mg,每日2次,两组疗程均为7—14天。结果试验组与对照组的临床有效率分别为84．61％与64．00％,细菌清除率分别为90．91％与66．67％,敏感茵百分率分别为93．18％与71．43％,听力下降发生率分别为1．79％与15．79％。以上结果经统计学处理两组差异有显著性。结论奈替米星为治疗下呼吸道感染的安全、有效的抗菌药物。