N-乙酰半胱氨酸抗X射线照射小鼠损伤效应

背景与目的：探讨N-乙酰左旋半胱氨酸(NAC)抗X线照射小鼠损伤效应。材料与方法： 通过预先给予NAC,观察其对受照小鼠的骨髓造血功能和免疫功能的影响。结果： NAC具有保护和提高受照小鼠骨髓有核细胞数,CFU-S,CFU-GM及胸腺细胞自发增殖能力和脾细胞产生白细胞介素(IL-2)的能力。结论： NAC可提高小鼠对X射线照射损伤的耐受能力。     

致癌物和X射线对人支气管上皮细胞的遗传毒理作用

从组织块长出的人支气管上皮细胞培养于MCDB151无血清培养基中,利用非程序性DNA合成(UDS)和微核试验检测化学致癌物和X射线对人支气管上皮细胞的遗传毒理作用。直接作用致癌物MNNG对所测试的7例上皮细胞均可分别引起UDS或微核增高,并具有剂量反应关系。X射线对4例都可引起微核增高。然而间接作用致癌物NNK和BaP引起的反应有明显个体差异。UDS试验中,NNK处理5例中有3例增高,BaP处理的4例中有3例增高。微核试验表明NNK处理的5例中3例为阳性,BaP处理4例中3例为阳性。本实验结果提示,NNK,BaP和X射线可能是人支气管上皮细胞潜在的致癌物。     

低剂量射线对肿瘤生物学影响及相关机制的研究进展

人类持续的暴露于低剂量的电离辐射,包括天然背景辐射穿透地球表面、医疗辐射、暴露于工业材料辐射等。有报道证明低剂量射线（low-dose radiation,LDR）可以在抗癌治疗中发挥促进组织修复、增强抗癌免疫、刺激氧化抗癌的作用;因此认识LDR对肿瘤的生物学影响及机制是十分有意义的。本文旨在总结LDR对肿瘤的生物学影响、相关信号通路、机制及其临床应用。     

铅暴露工人外周血淋巴细胞遗传损伤与端粒长度的改变

目的:探讨铅暴露工人外周血淋巴细胞遗传损伤情况与端粒长度改变之间的关系。方法:以珠三角某蓄电池厂的21名铅暴露工人为铅暴露组,26名无铅接触史的工人作为对照组。针对工人开展问卷调查并采集肝素抗凝外周血。检测工人外周血中血铅浓度、淋巴细胞的彗星试验指标、胞质分裂阻滞微核试验指标以及相对端粒长度改变情况。结果:铅暴露工人的血铅浓度为(3.08±1.86) mg/mL,与对照人群(0.26±0.25) mg/mL相比明显升高(P<0.05)。彗星试验中,铅暴露组工人的慧星尾长高于对照组(P<0.05);胞质分裂阻滞微核试验中,暴露组工人双核微核率和微核细胞率均高于对照组(P<0.05);铅暴露工人的外周血相对端粒长度较对照人群缩短(P<0.05)。相关分析结果显示,胞质阻滞微核试验的指标中双核微核率、微核细胞率、核桥率与工龄呈正相关(r_s分别为0.447、0.432、0.351,P均<0.05)。外周血相对端粒长度与工人工龄、血铅水平均呈负相关(r_s分别为-0.306、-0.394,P均<0.05)。结论:铅暴露可致工人外周血淋巴细胞的遗传损伤以及相对端粒长度的缩短。     

低剂量电离辐射诱导的EL-4细胞PARP-1蛋白表达及其意义的研究

目的:研究低剂量电离辐射诱导EL-4细胞适应性反应中PARP-1基因表达,为探讨低剂量电离辐射诱导适应性反应的DNA损伤修复机制提供实验依据.方法:将EL-4细胞分设空白对照组、较大剂量照射组(D2),其照射剂量分别为1、2和3 Gy以及诱导适应性反应照射组(D1+D2),其照射剂量分别为75 mGy+1 Gy、75 mGy+2 Gy和75 mGy+3 Gy,应用流式细胞仪和RT-PCR方法分别检测PARP-1基因蛋白及其转录水平表达.结果:单纯照射组PARP-1蛋白水平较对照组显著升高(P<0.01),预先给予75 mGy照射诱导的适应性反应组其PARP-1蛋白水平较大剂量照射组显著升高,P<0.01.PARP-1 mRNA水平表现出相同的变化.结论:PARP-1蛋白在诱导适应性反应照射组处于高表达,说明其在低剂量电离辐射诱导适应性反应中可能起重要作用.     

射线导致海马结构损伤及功能异常的研究现状

放射治疗是肿瘤三大治疗手段之一,尤其在头颈部肿瘤治疗中,已经成为部分肿瘤的根治性方法．由于照射靶区常难以避开正常脑组织,可能造成不同程度的放射性脑损伤．导致认知功能障碍。海马结构是颅内最易受射线损伤的与认知功能密切相关的天键结构,其受损机制和临床表脱是近年的研究热点：射线导致的海马结构损伤及其相关认知功能障碍越来越受到临床的重规。     

流式细胞术及染色体畸变分析在X射线职业照射者血细胞研究中的初步应用

本文用流式细胞术对５６例ｘ射线工作者的外周血细胞做了ＤＮＡ含量分析，并和染色体畸变结果进行了对比研究。结果表明，在５６例ｘ射线工作者小有５例出现ＤＮＡ倍体异常细胞。流式细胞术分析的高二倍体验出者，在其染色体数目分析中，２ｎ百分比与其呈一致性变化。Ｘ射线工作者的）２ｎ％（超二倍体细胞百分比）和ＳＰＦ（Ｓ期细胞百分比）均明显高于对照组（ｐㄑＯ．００５）．ｘ射线工作者染色体断裂率与）２ｃ％呈明显的正相关（ｒ＝０．８０）．     

线粒体DNA损伤与胃癌发生关系的研究

目的:检测胃癌线粒体DNA(mitochondrial DNA,mtDNA)的突变和不稳定性,探讨mtDNA损伤与胃癌发生的关系及其作用机制。方法:采用PCR扩增22例胃癌组织和对应的远端正常胃黏膜组织mtDNA控制区(D-loop)以及编码基因,利用变性高效液相色谱(denaturinghigh performance liquid chromatography,dHPLC)和DNA测序检测分析mtDNA的变异情况(包括种系性突变、体细胞突变和不稳定性)。结果:22例胃癌组织其线粒体不稳定性(mitochondrial genome instability,mtGI)的发生(13/22,59.1%)与mtDNA体细胞突变(10/22,45.5%)呈正相关,r=0.894 4,χ2(Pearson未校正法)=14.400 0,P=0.000 1。肠型胃癌患者12S rRNA位点损伤度(每例2.32个/1 000 bp)是弥漫型胃癌(每例0.86个/1 000 bp)的2.7倍,t=2.638 6,P=0.015 8。结论:mtDNA损伤可能参与肠型胃癌的发生,mtDNA损伤致癌可能需要2次打击激活。     

低剂量辐射对HCT-8大肠癌细胞周期的影响

目的 采用低剂量辐射免疫兴奋效应的动物模型,探讨低剂量X射线照射对人大肠癌HCT-8细胞株细胞周期的影响.方法 采用流式细胞术(FCM)检测大肠癌细胞周期.结果 低剂量电离辐射照射后,大肠癌G0/G1期细胞百分数升高(P＜0.05),S期细胞百分数降低(P＜0.05),G2 M期细胞百分数升高(P＜0.05).结论 低剂量电离辐射可抑制大肠癌细胞的DNA合成及增殖.     

碳酸锂对CEP方案的疗效及遗传损伤的抑制作用

目的 观察碳酸锂与CEP方案联合应用的疗效及对患者遗传损伤的抑制作用。方法101例实体瘤患者随机分为两组,治疗组(CEP方案+Li2CO3+基础用药)53例,对照组(CEP方案+基础用药)48例。疗程6周。结果 治疗组有效率为62.3％,对照组有效率为37.5％(P<0.05)。治疗组患者血中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和骨髓细胞核微粒(MNF)治疗前后比较差异有非常显著性(P<0.01);外周血白细胞治疗前后比较差异有显著性(P<0.05)。结论 碳酸锂能提高化疗药物CEP方案的疗效,并能减轻化疗药物对人体的损伤作用。     

ATM基因在低剂量电离辐射诱导EL-4细胞适应性反应中的作用

目的：探讨低剂量电离辐射诱导EL-4细胞适应性反应中ATM基因的作用。方法：EL-4细胞应用渥曼青霉素处理后接受低剂量0.075 Gy预先照射,再分别进行较高攻击剂量照射（1.0,1.5和2.0 Gy）,RT-PCR和免疫荧光法检测ATM mRNA及蛋白表达。同时应用流式细胞术检测细胞凋亡和周期进程变化。结果：渥曼青霉素能够阻断ATM基因在mRNA及蛋白水平的表达。应用渥曼青霉素后直接接受攻击剂量照射和应用渥曼青霉素后先接受低剂量0.075Gy预先照射后再接受攻击剂量照射,均能诱导EL-4细胞发生适应性反应。结论：ATM基因可能不影响低剂量电离辐射诱导EL-4细胞发生适应性反应。     

辐射诱导的旁观者效应研究进展

直接受到照射的细胞通过信号转导引起临近细胞的损伤,称为旁观者效应。其具体机制非常复杂,目前仍不完全清楚。本文从旁观者效应对细胞DNA损伤的类型,旁观者效应中的分子信号转导及体内存在的旁观者效应等不同方面进行综述。     

辐射诱导的旁观者效应研究进展

直接受到照射的细胞通过信号转导引起临近细胞的损伤,称为旁观者效应.其具体机制非常复杂,目前仍不完全清楚.本文从旁观者效应对细胞DNA损伤的类型,旁观者效应中的分子信号转导及体内存在的旁观者效应等不同方面进行综述.     

Exposure to low dose ionising radiation: Molecular and clinical consequences

This review article provides a comprehensive overview of the experimental data detailing the incidence, mechanism and significance of low dose hyper-radiosensitivity (HRS). Important discoveries gained from past and present studies are mapped and highlighted to illustrate the pathway to our current understanding of HRS and the impact of HRS on the cellular response to radiation in mammalian cells. Particular attention is paid to the balance of evidence suggesting a role for DNA repair processes in the response, evidence suggesting a role for the cell cycle checkpoint processes, and evidence investigating the clinical implications/relevance of the effect.     

Exposure to low dose ionising radiation: Molecular and clinical consequences

This review article provides a comprehensive overview of the experimental data detailing the incidence, mechanism and significance of low dose hyper-radiosensitivity (HRS). Important discoveries gained from past and present studies are mapped and highlighted to illustrate the pathway to our current understanding of HRS and the impact of HRS on the cellular response to radiation in mammalian cells. Particular attention is paid to the balance of evidence suggesting a role for DNA repair processes in the response, evidence suggesting a role for the cell cycle checkpoint processes, and evidence investigating the clinical implications/relevance of the effect.     

DNA base damage induced by ionizing radiation recognized by Escherichia coli UvrABC nuclease but not Nth or Fpg proteins

Ionizing radiation and other free radical-generating systems induce a great variety of oxidative damage to DNA bases. The major known lesions are repaired by two well-characterized DNA glycosylases of Escherichia coli, endonuclease III (Nth) and formamidopyrimidine-DNA glycosylase (Fpg), which have associated AP lyase activities. To detect and characterize potentially harmful oxidative base DNA lesions that may be repaired by alternative means, we exposed plasmid DNA to low doses γ-rays and removed the major base lesions by treatment with Nth and Fpg proteins. The closed circular DNA remaining after these treatments was used as a substrate of the UvrABC endonuclease complex from E. coli and as a template in a DNA polymerase arrest assay in vitro. The circular DNA contained lesions that were recognized and incised by the UvrABC nuclease and also lesions that blocked DNA polymerization in vitro. The blocking lesions were more abundant in DNA irradiated under nitrogen than under air and occurred mainly at tandem guanines; however, they were also frequent at tandem adenines and tandem cytosines. © 1996 Wiley-Liss, Inc.     

低剂量电离辐射对小鼠肿瘤转移及免疫功能的影响

 C₅₇BL/6,小鼠眼静脉注射B16黑色素瘤细胞24小时后，进行75mGyX线全身一次照射，结果显示，照射后小鼠的肺转移结节数明显低于对照组。机体免疫功能比对照组明显增强。     

Single extreme low dose/low dose rate irradiation causes alteration in lifespan and genome instability in primary human cells

To investigate the long-term biological effect of extreme low dose ionising radiation, we irradiated normal human fibroblasts (HFLIII) with carbon ions (290 MeV u(-1), 70 keV microm(-1)) and gamma-rays at 1 mGy (total dose) once at a low dose rate (1 mGy 6-8 h(-1)), and observed the cell growth kinetics up to 5 months by continuous culturing. The growth of carbon-irradiated cells started to slow down considerably sooner than that of non-irradiated cells before reaching senescence. In contrast, cells irradiated with gamma-rays under similar conditions did not show significant deviation from the non-irradiated cells. A DNA double strand break (DSB) marker, gamma-H2AX foci, and a DSB repair marker, phosphorylated DNA-PKcs foci, increased in number when non-irradiated cells reached several passages before senescence. A single low dose/low dose rate carbon ion exposure further raised the numbers of these markers. Furthermore, the numbers of foci for these two markers were significantly reduced after the cells became fully senescent. Our results indicate that high linear energy transfer (LET) radiation (carbon ions) causes different effects than low LET radiation (gamma-rays) even at very low doses and that a single low dose of heavy ion irradiation can affect the stability of the genome many generations after irradiation.     

Low-dose ionizing radiation induces mitochondrial fusion and increases expression of mitochondrial complexes I and III in hippocampal neurons

High energy ionizing radiation can cause DNA damage and cell death. During clinical radiation therapy, the radiation dose could range from 15 to 60 Gy depending on targets. While 2 Gy radiation has been shown to cause cancer cell death, studies also suggest a protective potential by low dose radiation. In this study, we examined the effect of 0.2-2 Gy radiation on hippocampal neurons. Low dose 0.2 Gy radiation treatment increased the levels of MTT. Since hippocampal neurons are post-mitotic, this result reveals a possibility that 0.2 Gy irradiation may increase mitochondrial activity to cope with stimuli. Maintaining neural plasticity is an energy-demanding process that requires high efficient mitochondrial function. We thus hypothesized that low dose radiation may regulate mitochondrial dynamics and function to ensure survival of neurons. Our results showed that five days after 0.2 Gy irradiation, no obvious changes on neuronal survival, neuronal synapses, membrane potential of mitochondria, reactive oxygen species levels, and mitochondrial DNA copy numbers. Interestingly, 0.2 Gy irradiation promoted the mitochondria fusion, resulting in part from the increased level of a mitochondrial fusion protein, Mfn2, and inhibition of Drp1 fission protein trafficking to the mitochondria. Accompanying with the increased mitochondrial fusion, the expressions of complexes I and III of the electron transport chain were also increased. These findings suggest that, hippocampal neurons undergo increased mitochondrial fusion to modulate cellular activity as an adaptive mechanism in response to low dose radiation.     

甲基化芯片检测电离辐射诱导人外周血淋巴细胞DNA甲基化水平的变化

目的：筛选正常人细胞基因组中电离辐射后甲基化水平发生变化的基因,为在其中寻找新型辐射损伤标志物奠定研究基础。方法：⁶⁰Co γ射线照射人外周血全血,照射剂量为0、0.5和2.0 Gy。利用Illumina 450K芯片检测外周血淋巴细胞基因组DNA甲基化水平的变化,筛选甲基化水平差异的基因,利用GO功能富集分析基因的分子功能和参与的生物学途径。结果：0.5和2.0 Gy γ射线照射下人外周血淋巴细胞基因组DNA甲基化水平显著上调的基因有1 311个,显著下调的基因286个。GO功能富集分析表明,按富集度大小排列,差异基因在生物途径水平上排在首位的是“细胞过程”（富集度=5.86）,在细胞定位水平上排在首位的是“细胞”（富集度=7.48）,在分子功能水平上排在首位的是“结合”（富集度=5.27）。进一步细分后得到差异基因显著富集在与转录调控及转录因子活性相关的功能上,与以往的研究结果认为DNA甲基化参与转录调控和基因表达相一致;甲基化水平差异基因还显著富集在核苷连接（GO：0001882）上,并在其中寻找到与DNA修复相关的基因RAD50、RAD54L和INIP,以及与维持染色体结构稳定相关的基因HIST1H4K、SMC1B。结论：正常人外周血淋巴细胞基因甲基化水平受电离辐射影响,可进一步研究将这些与DNA修复、维持染色体结构稳定相关的基因甲基化水平作为辐射损伤标志物的可行性。