低剂量辐射诱导适应性反应的分子机制研究现状

低剂量辐射(low dose radiation，LDR)可以增强细胞对随后进行的攻击性剂量(challenge dose)照射的抵抗能力，从而降低攻击性照射引起的染色体畸变和DNA损伤。人们把LDR的这种效应称之为“低剂量辐射诱导的适应性反应”。低剂量辐射诱导适应性反应的分子机制主要涉及细胞信号转导、ROS(活性氧物质)的作用和DNA修复兴奋效应等方面。     

低剂量辐射与糖尿病

低剂量辐射(LDR)诱导免疫兴奋效应及适应性反应的机制可能与LDR诱导的保护性蛋白和抗氧化物质有关,并在糖尿病(DM)及其他疾病中具有明显的治疗效果。主要综述LDR对DM发生发展及其并发症的作用和可能的机制,并讨论LDR应用于临床及DM并发症的前景。     

低剂量辐射的细胞遗传适应性反应机理研究现状

很多学者对LDR(低剂量辐射)可以在体内及体外培养的细胞中诱导出适应性反应的机理进行了深入的研究,发现适应性反应的诱导与很多因素有关,这些因素包括LDR诱导的DNA修复系统的激活、LDR诱导的基因和蛋白的作用、抗氧化物酶的作用、细胞信号转导以及与p53蛋白有关的细胞周期阻滞的影响等。     

低剂量辐射刺激作用的实验研究

本文报告低剂量,低LET辐射对小鼠免疫功能、染色体畸变和DNA损伤修复影响的实验资料。低剂量单次x线或持续γ线全身照射后,出现辐射刺激效应,表现为(1)增强免疫功能,包括抗体形成反应增强、自介素2产生增多、NK活性增高、胸膜细胞增殖加快和ConA诱导的大分子合成激活,(2)诱导细胞遗传学适应性反应,即低剂量辐射预先作用使相继较大剂量所致染色体损伤减轻； (3)促进DNA修复,包括非程序DNA合成增强和DNA聚合酶活性增高。对辐射刺激效应的发生机理和意义进行了讨论。     

低剂量辐射诱导蛋白对正常人外周血淋巴细胞亚群的刺激效应

目的 探讨低剂量辐射(LDR)诱导蛋白对淋巴细胞亚群功能的影响。方法 观察LDR诱导蛋白对单克隆抗体铺皿法—直接法分离出的淋巴细胞亚群CD4、CD8、CDl9细胞转化功能的影响。结果 经LDR诱导蛋白作用后，亚群细胞14C—TdR掺入值增高，分别为对照组的118．23％、115．18％和121．62％。结论 LDR诱导蛋白能不同程度地刺激CD4、CD8、CDl9细胞DNA合成。     

低剂量辐射联合环磷酰胺对肿瘤细胞凋亡、细胞周期以及骨髓增殖的影响

目的　探讨低剂量辐射联合环磷酰胺对小鼠移植肿瘤细胞的凋亡、细胞周期以及骨髓增殖的影响。方法　昆明种雄性小鼠随机分为空白对照组、荷瘤对照组 (假照组 )、低剂量照射组(LDR组 )、CTX化疗组 (CTX组 )和低剂量照射联合化疗组 (LDR CTX组 ) ,左后肢腹股沟皮下接种S180肉瘤细胞 ,接种后第 5 ,8天γ射线全身照射 75mGy ,照射后 36h采用环磷酰胺 (CTX)化疗 ,测量肿瘤大小变化 ,并取肿瘤组织经流式细胞仪分析细胞凋亡、细胞周期 ,取冲洗骨髓组织分析骨髓增殖情况。结果　与假照组相比 ,各处理组肿瘤生长缓慢。LDR组肿瘤细胞凋亡增加 ,CTX组、LDR CTX组G1 期细胞比例明显增加 ,S期细胞比例明显减少 (P <0 0 5 )。与空白对照组相比 ,假照组、低剂量照射组骨髓细胞浓度未见明显变化 ,化疗组 (CTX组、LDR CTX组 )明显减少 (P <0 0 0 1) ;增殖指数 (PI)CTX组、LDR CTX组明显增加 ,LDR CTX组比CTX组高。结论　低剂量辐射联合环磷酰胺可使机体肿瘤细胞G1 期阻滞加剧 ,对肿瘤增殖细胞杀伤作用增强 ,明显提高机体抗肿瘤的作用 ,同时保护机体的骨髓造血机能 ,具有辅助肿瘤化疗的实际临床意义。     

低剂量电离辐射对高剂量辐射致癌的影响

低剂量辐射 (LDR)免疫增强效应及其诱导的适应性反应已得到大量实验研究和人体观察资料证实 ,其生物学意义引起许多学者的关注[1 5 ]。免疫系统是机体防御系统的重要组成部分 ,特别是免疫监视作用在肿瘤发生、发展和转归上起着十分重要的作用。因此LDR免疫增强效应及其诱导的适应性反应对机体抗肿瘤能力影响的研究具有重要的理论和临床意义。本研究较系统地探讨了LDR对高剂量辐射诱发小鼠胸腺淋巴瘤 (TL)的影响及其免疫学机理 ,其结果对评价LDR对机体健康影响及在临床上的应用具有重要的意义。一、材料和方法1 动物 :雌性C57BL 6J纯…     

低剂量辐射的细胞遗传适应性反应机理研究现状

很多学对LDR（低剂量辐射）可以在体内及体外培养的细胞中诱导出适应性反应的机理进行了深入的研究，发现适应性反应的诱导与很多因素有关，这些因素包括LDR诱导的DNA修复系统的激活、LDR诱导的基因和蛋白的作用、抗氧化物酶的作用、细胞信号转导以及与p53蛋白有关的细胞周期阻滞的影响等。     

低剂量照射在肿瘤治疗中的应用研究进展

电离辐射生物效应与辐射剂量和剂量率有关,大、中剂量照射以损伤效应为主,低剂量照射可诱导机体的兴奋效应、适应性反应、超敏感性、旁效应等。低剂量全身照射通过诱导免疫增强效应、超敏感性、激活抗氧化酶系统及肿瘤细胞凋亡等机制具有抗肿瘤作用,降低随后较大剂量辐射诱发的肿瘤发生率。目前。低剂量照射在肿瘤防治中的应用正成为研究的热点。     

低剂量辐射对人骨髓间充质干细胞影响的研究

目的 探讨低剂量辐射(LDR)对人骨髓间充质干细胞(hBM-MSC)生物学特性的影响。方法 应用体外培养传代的第四代hBM-MSC,采用X射线照射,照射剂量分别为50 mGy、75mGy、100 mGv,剂量率为12.5 mGy/min,分别观察LDR后hBM-MSC生长曲线、细胞周期与凋亡的变化及细胞因子、干细胞因子(SCF)、白细胞介素6(IL-6)、巨噬细胞集落刺激因子(M-CSF)表达量的变化。结果 LDR后,hBM-MSC从72 h起生长明显加快;LDR照射hBM-MSC后,在G0-G1期百分率逐渐减少,S期百分率在照射后48 h、72 h逐渐明显增多,以75 mGy照射后72 h的S期百分率增多最明显,为68.88%,而细胞凋亡的变化结果是LDR后在24 h、48 h有增多趋势,照射后72 h,凋亡细胞百分率有减少趋势;LDR照射hBM。MSC后24 h、48 h SCF分泌量均有升高趋势;50mGv、75mgy、100mGyX射线照射hBM-MSC后在培养的24 h、48 h,IL-6分泌量均有升高趋势;LDR照射hBM-MSC后,除50mGy照射后72h外,M-CSF分泌量在不同剂量照射后24 h、48 h、72 h均持续升高。结论 LDR后hBM-MSC从生长曲线、细胞周期与凋亡的变化及细胞因子表达量的变化均表现出兴奋性效应。     

低水平环境因子与适应性反应

简要叙述了低水平环境因子诱导适应性反应的研究现状。强调了极低剂量率电离辐射诱导适应性反应的可能及其剂量效应和时间效应关系的特点。分析了低水平电离辐射诱导适应性反应机理研究的最新进展。讨论了低水平环境因子诱导适应性反应科学资料的实际应用前景。提出了今后进一步研究的建议     

Adaptive response and human benefit: Part I. A microdosimetry dose-dependent model

PURPOSE: It is important to evaluate how adaptive response may be of human benefit from the risks of ionizing radiation. The purpose of this work is to develop and apply a microdosimetric dose response model capable of explicitly determining, for broad beam exposures, the threshold and progressive activation of natural spontaneous and radiation damage protective mechanisms associated with adaptive response and other cellular negative response behavior. MATERIALS AND METHODS: A biophysical model was developed quantifying the accumulation of Poisson distributed microdose specific energy hits to cell critical nucleus volumes. The model was applied to the adaptive response data of Wiencke et al., Redpath et al., Azzam et al. and Pohl-Ruling et al. The model was also applied to non-adaptive response data showing dose response reductions below the zero dose natural spontaneous level and to data exhibiting mid-range non-monotonic dose response plateaus. RESULTS: We find good fits of the model to all data. For adaptive response, a significant result is, that only one or two specific energy hits of low linear energy transfer (LET) radiation in the cell nucleus activates the protective mechanisms for both the natural spontaneous and radiation damage. Several data support a dose plateau for radon progeny alpha production of chromosome aberrations in human lymphocytes. Using the model, a bystander factor of about 30 is obtained with the model for high dose rate, in vitro alpha particle data. For low dose rate in vivo, the bystander effect is minimal suggesting for alphas that the bystander effect may be dose rate dependent. There is no evidence of bystander effects in the low LET adaptive response data analysis. CONCLUSIONS: The microdosimetry model allows concise determinations of specific energy hits within the cell critical nucleus volume to activate both protective and damage mechanisms. One or two low LET hits can result in reduction of both zero dose natural spontaneous and radiation-induced, carcinogenic causing damage. The model should be useful in comparing in vitro and in vivo broad beam to single track microbeam exposure data. The model is capable of determining, to an accuracy of +/- one specific energy hit, the minimum threshold for induction of radioprotective mechanisms--crucial to assessing the potential human benefit of adaptive response and other negative dose response behavior.     

Mapping the research trends on the biological effects of radiation less than 100 mSv: a bibliometric analysis for 30 years publication

Abstract

Purpose: The purpose of this study is to evaluate the global scientific publication of biological research of low dose radiation for the past 30 years and provide the insights into the characteristics of research activities and major topics regarding biological effects of low dose radiation exposure.

Materials and methods: We bibliometrically investigated the biological research publication of radiation exposure less than 100 mSv. References published from 1987 to 2016 were achieved from the Scopus database and filtered by several criteria such as publication types, research fields, and radiation dose range.

Results: Total 753 references were assembled for the bibliometric analysis on the biological studies of radiation effect less than 100 mSv. It provided fundamental knowledge of research, including production tendency, contribution, impact journals, and major research themes. Based on the keyword analysis, we found that specific topics on the biological response to radiation exposure have been changed from the examination of low dose radiation-induced phenomena to the investigation of how to induce a physiological response. In addition, featured articles showed the various views on the biological effects of radiation less than 100 mSv in 30 years publication, depending on radiation doses and types.

Conclusions: Continuous studies in large programs of low dose radiation led to the increment of research achievements in accordance with societal needs in radiation safety regulation for health protection. Our findings can surely help radiation researchers to gain insights and penetration in low dose risk research for radiation protection, and establish a further research direction.     

Unresectable non-oat cell carcinoma of the lung: definitive radiation therapy

Between 1976 and 1983, 267 patients with non-oat cell carcinoma of the lung were treated with radiation therapy alone. One hundred thirty-four patients had squamous cell carcinoma; 69, large cell carcinoma; and 64, adenocarcinoma. Stage III carcinoma was diagnosed in 87% of the patients. Total radiation dose was less than 45 Gy in 69 patients (low dose group), 45-55 Gy in 161 (middle dose group), and 55-65 Gy in 37 (high dose group); dosage was 180-200 cGy daily, 5 days per week. Minimum follow-up was 3 years (median, 6 years). Tumor control within the radiation fields was achieved in 12%, 43%, and 78% of the low, middle, and high dose groups, respectively. A complete response rate of 13%, 23%, and 35% and an overall response of 43%, 71%, and 86% were seen in the low, middle, and high dose groups, respectively. The 5-year recurrence-free survival rate for all patients was 7% and was dependent on radiation dose and tumor response. This study indicates that tumor control and complete response rates are improved with a radiation dose of 55-65 Gy and that complete responders have improved survival.     

低剂量辐射增强大剂量辐射对人胶质瘤的抑瘤作用

目的 探讨低剂量辐射及低剂量联合大剂量辐射对人胶质瘤生长的影响。方法 以胶质瘤细胞株U251及荷人胶质瘤裸鼠移植瘤为研究对象,分别给予低剂量辐射和低剂量联合大剂量辐射,采用细胞计数、噻唑蓝(MTT)、流式细胞术等方法检测对细胞增殖的影响,通过计算抑瘤率来观察低剂量辐射联合大剂量辐射对移植瘤生长的影响。结果 低剂量辐射后U251细胞计数、MTT及流式细胞术检测结果与假照组相比差异无统计学意义;大剂量辐射组及低剂量联合大剂量辐射组细胞增殖明显受抑,凋亡增多,细胞周期G₂期阻滞,两组间差异无统计学意义;低剂量辐射联合大剂量辐射组与单独大剂量辐射组均对裸鼠移植瘤有明显的抑制作用,但联合照射组抑瘤作用更强;联合照射组与单纯大剂量辐射组相比,血液系统损伤有所减轻。低剂量辐射组与假照组相比肿瘤生长差异无统计学意义。结论 低剂量辐射对人胶质瘤细胞无直接的抑制作用、兴奋效应,不诱导对大剂量辐射适应性反应,但能够在对正常造血系统产生保护作用的基础上,增强大剂量辐射对荷瘤裸鼠移植瘤的抑瘤作用,这种协同抗肿瘤作用在去除细胞免疫影响后仍然存在。     

Preclinical animal research on therapy dosimetry with dual isotopes

Preclinical research into radionuclide therapies based on radiation dosimetry will enable the use of any LET-equivalent radionuclide. Radiation dose and dose rate have significant influence on dose effects in the tumour depending on its radiation sensitivity, possibilities for repair of sublethal damage, and repopulation during or after the therapy. Models for radiation response of preclinical tumour models after peptide receptor radionuclide therapy based on the linear quadratic model are presented. The accuracy of the radiation dose is very important for observation of dose-effects. Uncertainties in the radiation dose estimation arise from incomplete assay of the kinetics, low accuracy in volume measurements and absorbed dose S-values for stylized models instead of the actual animal geometry. Normal dose uncertainties in the order of 20% might easily make the difference between seeing a dose-effect or missing it altogether. This is true for the theoretical case of a homogeneous tumour type behaving in vivo in the same way as its cells do in vitro. Heterogeneity of tumours induces variations in clonogenic cell density, radiation sensitivity, repopulation capacity and repair kinetics. The influence of these aspects are analysed within the linear quadratic model for tumour response to radionuclide therapy. Preclinical tumour models tend to be less heterogenic than the clinical conditions they should represent. The results of various preclinical radionuclide therapy experiments for peptide receptor radionuclide therapy are compared to the outcome of theoretical models and the influence of increased heterogeneity is analysed when the results of preclinical research is transferred to the clinic. When the radiation dose and radiobiology of the tumour response is known well enough it may be possible to leave the current phenomenological approach in preclinical radionuclide therapy and start basing these experiments on radiation dose. Then the use of a gamma ray-emitting radionuclides for a chemically comparable beta-particle-emitting paired isotope for therapy evaluation would be feasible.     

Symposium of ICRP Committee I

Since the publication of ICRP new recommendation,Chinese scientists in the field of radiation protection,radiobiology. Health physics and radiation dosimetry have paid great attention tO it Series of symposiums and workshops were held to introduce and discuss the new recommendation Of course,many questions were raised which focused on the quantitative estimation of radiation risk and the biological bases of the new dose limits,es. Peciatly the dose response model,risk projection model in life span time,transfer of risk from one population to another,the extrapolation from high dose and high dose rate to low dose and low dose rate,the adoption of DDREF,and some new terms of quantity and unit were discussed more extensively and deeply.     

Radiation-induced bystander effects: are they good, bad or both?

Our current knowledge of the mechanisms underlying the induction of bystander effects by low dose-low linear-energy-transfer ionising radiation is reviewed, and the question of how bystander effects may be related to observed adaptive responses, systemic genomic instability or other effects of low doses exposures is considered. Bystander effects appear to be the result of a generalised stress response in tissues or cells. The signals may be produced by all exposed cells but the response may require a quoram in order to be expressed. The major response involving low LET radiation exposure discussed in the existing literature is a death response, which has many characteristics of apoptosis but may be detected in cell lines without p53 expression. While a death response might appear to be adverse, it can in fact be protective and remove damaged cells from the population. Since many cell populations carry damaged cells without being exposed to radiation ('background damage') low doses exposures might cause removal of cells damaged by agents other than the test dose of radiation, which would lead to the production of 'u- or n-shaped' dose-response curves. The level of harmful or beneficial response would then be related to the background damage carried by the cell population and the genetic programme determining response to damage. This model may be important when attempting to predict the consequences of mixed exposures involving radiation and other environmental stressors.     

不同剂量辐射诱导小鼠胸腺Th1-Th2-Th3型细胞相关基因的功能分析

目的 应用功能分类基因芯片技术,分析高、低剂量全身照射对小鼠胸腺细胞中Th1、Th2及Th3/Tr1各亚型功能相关基因的差异表达,探讨辐射免疫效应的分子机制.方法 健康ICR小鼠按随机数字表法分为低剂量组(0.075 Gy)、高剂量组(2.0 Gy)和假照组,于照射后16 h处死小鼠取胸腺组织,应用细胞因子与炎症反应PCR芯片技术进行Th1-Th2-Th3功能分类芯片分析.结果 低剂量(0.075 Gy)X射线全身照射后小鼠胸腺细胞中有8个基因表达上调,5个基因表达下调;高剂量(2.0 Gy)X射线全身照射后小鼠胸腺细胞中有54个基因表达上调,3个基因表达下调.具体有Th型细胞相关基因、Th2型细胞相关基因、Th3/Tr1型细胞相关基因、Th1/Th2型免疫应答基因以及转录因子相关基因.其中,低剂量辐射诱导胸腺中的Th1型细胞相关基因Stat4和Socs1的表达上调,而对Th2型和Th3/Tr型细胞相关基因IL-4ra、Cebpb、Gata3及Tgfb3下调,最终导致Th1型免疫应答基因Sftpd上调.高剂量辐射均可诱导Th1、Th2和Th3/Tr型细胞相关基因的上调,但Th1型免疫应答基因表达无变化,而Th2型免疫应答相关基因Cd86、IL-18、IL-10以及Irf4上调.结论 低剂量辐射诱导Th1型免疫应答,而高剂量辐射诱导Th2型免疫应答.