低剂量电离辐射诱导细胞凋亡适应性反应研究进展

根据联合国原子辐射效应科学委员会(UNSCEAR) 1986年的报告,低剂量辐射(LDR)是指0.2Gy以内的低传能线密度(LET)辐射或0.05 Gy以内的高LET辐射.目前,科学界对LDR的健康影响问题存在两种不同的理论,一是随机性效应的线性无阈理论(LNT),二是在低剂量范围内有阈的适应性反应(AR)理论.许多实验表明,LDR可以刺激多种细胞功能,包括繁殖与修复功能、免疫增强效应及体内激素平衡的改变等,这类效应被称为低剂量刺激效应或兴奋效应(Stimulation effect or hormesis) [1 -2].     

低剂量辐射适应性反应机制研究进展

目前，对较大或高剂量辐射所引起的生物学效应已经有了充分的认识，而对低剂量辐射所引起生物学效应的认识还很局限。研究表明适应性反应是低剂量辐射诱导细胞产生的效应之一，并涉及DNA损伤反应、免疫/炎症反应和抗氧化反应等多种机制。本文就低剂量辐射适应性反应机制的研究进展进行综述，为相关研究人员提供理论基础。     

辐射生物效应多样性的统一辐射剂量生物效应理论模型和应用研究

目的 试图从理论上提出辐射生物效应多样性的辐射剂量生物效应理论,建立统一的全剂量辐射生物效应理论模型,定量描述和解释辐射生物效应的多样性。方法 总结提出辐射剂量生物效应理论的6个原理的基础上,建立统一剂量辐射生物效应理论模型。结果 提出辐射生物效应多样性的辐射剂量生物效应理论,建立了8个辐射剂量生物效应方程,可以定量描述和解释辐射生物效应的多样性。结论 建立的辐射剂量生物效应理论和理论模型,定量描述和解释辐射剂量生物效应:一般损伤效应、低剂量兴奋性效应、旁效应和超敏效应。该理论和理论模型适用于其它广义刺激:物理因子、化学因子、生物因子、心理、药物、毒物、信息等剂量生物效应关系,可称为广义刺激剂量生物效应理论模型,具有重要的学术意义和应用价值。     

RNA相关的低剂量辐射响应标志物

电离辐射会对人体造成损伤,根据受照剂量、时间等因素的不同可诱发多种生物效应.目前对于低剂量辐射产生的健康效应仍有争议,筛选对低剂量敏感的辐射响应生物标志物,对于完善低剂量辐射生物效应机制、拓宽低剂量辐射在临床中的应用均具有重要理论意义.综述探讨各核糖核酸(RNA)在低剂量辐射反应中的变化及其对辐射敏感性的调节作用,同时...     

低剂量辐射的兴奋效应和适应性反应及在肿瘤学方面的研究进展

低剂量辐射(low dose radiation，LDR)对机体的兴奋作用指受到LDR后机体出现的免疫力增强、生育能力提高及对肿瘤的抵抗力加强等效应，适应性反应指小剂量的预先照射能使机体对其后的大剂量照射产生适应，可减轻大剂量照射引起的损伤或后果。目前的研究提示，LDR的预先照射可提高其后大剂量放疗的效果；小剂量的X射线预先愚射，有抑制荷瘤小鼠肿瘤生长趋势，促进荷瘤小鼠的局部放疗效果的作用，而且多次低剂量预照射的效果比一次顶照射好。在恶性淋巴瘤患者中进行临床试验的结果也得出了相同的结论；对高本底地区居民和医疗受照人群如肺结核患者等的流行病学调查也证实，他们总的癌症患病率并没有升高。LDR对肿瘤影响机理尚不清楚。有学者认为免疫功能受低剂量照射所激活是LDR抗肿瘤作用的基础，而更多的学者倾向于认为LDR可激活DNA的修复系统，表现为接受LDR后可使其后接受大剂量照射造成的染色体畸变减少，并通过修复酶活性的检测得到证实。     

低剂量电离辐射长期接触健康效应研究进展

随着核能的发展及电离辐射的广泛应用,接触低剂量电离辐射的职业人群和公众越来越多,低剂量电离辐射接触对人群健康效应包括致癌、非致癌等研究成为公共卫生领域研究的热点。低剂量电离辐射引起的各种生物效应主要取决于辐射的物理性质、接触时间、剂量和剂量率等。目前关于低剂量电离辐射长期接触对人群的健康效应研究结论尚无一致共识。本文就国内外关于低剂量电离辐射长期接触的健康效应研究进行回顾,为低剂量电离辐射长期接触人群的健康效应、影响机制及防护策略研究等提供科学基础。     

低剂量辐射对T细胞CD28和Fas分子表达作用的研究

目的 研究低剂量辐射对T细胞CD38受体分子和Fas受体表达的适应性反应，探讨低剂量辐射免疫兴奋效应的分子机制。方法 采用直接免疫荧光－流式细胞仪分析技术，测定低剂量γ射线辐射后T细胞CD28受体分子和Fas受体（CD95）表达的变化。用JAM检测技术研究低剂量γ射线辐射后T细胞DNA断裂程度。结果 用低剂量γ射线诱导辐射后，正常人CD3^ T细胞CD28受体分子的表达有所增加；先低剂量辐射再高剂量辐射，CD28受体分子的表达无明显下降，Fas受体的表达和T细胞DNA断裂程度低于单纯高剂量照射组。结论 低剂量γ射线辐射增加CD28受体分子的表达，先低剂量γ射线辐射再高剂量辐射，CD28受体分子、Fas受体分子的表达和T细胞DNA断裂程度存在适应性反应，这可能是低剂量辐射的免疫兴奋效应的分子机制之一。     

低剂量辐射后小鼠骨髓白血病细胞凋亡的观察

目的 观察低剂量辐射(LDR)后不同时间小鼠骨髓白血病细胞凋亡的变化,探讨全身低剂量辐射辅助治疗白血病的理论依据。方法 将小鼠粒单白血病细胞系WEH I-3尾静脉接种于BALB/c小鼠建立白血病动物模型。将60只成功建立的粒单白血病模型小鼠,对半分为对照组和实验组。对照组小鼠不进行照射,实验组小鼠同时给予75mGy的LDR。于LDR后1d、2d、3d、5d和10d分别处死实验组及对照组6只小鼠,取其骨髓,通过荧光显微镜、电镜观测骨髓白血病细胞的凋亡情况。结果 实验组小鼠LDR后第2d、3d骨髓白血病细胞凋亡率最高,5d和10d次之,与对照组比较差异显著(P均<0.05)。结论 LDR可使白血病小鼠骨髓肿瘤细胞凋亡率增加,其作用机制明显不同于大剂量射线治疗对肿瘤细胞的杀伤,可能与LDR增加白血病小鼠免疫兴奋效应,促进某些细胞因子分泌有关。     

低剂量辐射联合环磷酰胺对荷瘤鼠DNA损伤的影响

目的研究低剂量辐射联合环磷酰胺对荷瘤鼠外周血淋巴细胞DNA损伤的影响。方法荷瘤鼠随机分为对照组、CTX化疗组(CTX组,40mg/kg)和低剂量照射联合CTX组(LDR CTX组),环磷酰胺给予前6h行5cGy的低剂量照射,连续3 d。采用中性单细胞凝胶电泳检测低剂量辐射联合化疗后对荷瘤鼠外周血淋巴细胞DNA双链断裂的情况。观察了尾长、彗星长、头DNA%、尾DNA%、尾矩、Olive尾矩等指标的变化。结果LDR CTX组其尾长、彗星长、头DNA%、尾DNA%、尾矩、Olive尾矩均比CTX组明显减小,各项指标差异均有显著性(P<0.05)。结论荷瘤鼠预先接受低剂量全身照射能减轻环磷酰胺治疗后外周血淋巴细胞DNA损伤。     

电离辐射对职业照射生物效应影响的调查研究

目的 探讨长期低剂量电离辐射对人体的生物效应,为综合防治提供依据。方法 对滨州市各类辐射工作人员378人进行了受照剂量测定,临床查体,实验室检查,并设非辐射人员102人为对照组。结果 受检者人均年剂量当量为0.98 mSv。12.6%的辐射人员有头晕、乏力、记忆力减退等症状,体征有齿龈出血,手部皮肤和指甲改变,眼晶状体混浊等,均高于对照组(P <0.01)。WBC低于4.0×10⁹/L的检出率为3.9%。ALT>40IU/L的占2.3%,HBsAg阳性率为6.1%,低于对照组的11.7%。T淋巴细胞亚群水平普遍下降,与对照组比较,差异有非常显著性(P< 0.01)。外周血CA、MC均明显高于对照组,且随工龄及剂量的增加而增高。血清中单项Ig增高30人,占7.9%,辐射组的IgG高于对照组(P < 0.01)。表明长期低剂量电离辐射发生的生物效应,是损伤和修复交替进行的过程。结论 长期低剂量电离辐射具有一定的辐射损伤效应,亦具有刺激生物免疫机能的效应。     

Chronic low-dose γ-irradiation of Drosophila melanogaster larvae induces gene expression changes and enhances locomotive behavior

Although radiation effects have been extensively studied, the biological effects of low-dose radiation (LDR) are controversial. This study investigates LDR-induced alterations in locomotive behavior and gene expression profiles of Drosophila melanogaster. We measured locomotive behavior using larval pupation height and the rapid iterative negative geotaxis (RING) assay after exposure to 0.1 Gy γ-radiation (dose rate of 16.7 mGy/h). We also observed chronic LDR effects on development (pupation and eclosion rates) and longevity (life span). To identify chronic LDR effects on gene expression, we performed whole-genome expression analysis using gene-expression microarrays, and confirmed the results using quantitative real-time PCR. The pupation height of the LDR-treated group at the first larval instar was significantly higher (∼2-fold increase in PHI value, P < 0.05). The locomotive behavior of LDR-treated male flies (∼3 − 5 weeks of age) was significantly increased by 7.7%, 29% and 138%, respectively (P < 0.01), but pupation and eclosion rates and life spans were not significantly altered. Genome-wide expression analysis identified 344 genes that were differentially expressed in irradiated larvae compared with in control larvae. We identified several genes belonging to larval behavior functional groups such as locomotion (1.1%), oxidation reduction (8.0%), and genes involved in conventional functional groups modulated by irradiation such as defense response (4.9%), and sensory and perception (2.5%). Four candidate genes were confirmed as differentially expressed genes in irradiated larvae using qRT-PCR (>2-fold change). These data suggest that LDR stimulates locomotion-related genes, and these genes can be used as potential markers for LDR.     

Diminished or inversed dose-rate effect on clonogenic ability in Ku-deficient rodent cells

The biological effects of ionizing radiation, especially those of sparsely ionizing radiations like X-ray and γ-ray, are generally reduced as the dose rate is reduced. This phenomenon is known as ‘the dose-rate effect’. The dose-rate effect is considered to be due to the repair of DNA damage during irradiation but the precise mechanisms for the dose-rate effect remain to be clarified. Ku70, Ku86 and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are thought to comprise the sensor for DNA double-strand break (DSB) repair through non-homologous end joining (NHEJ). In this study, we measured the clonogenic ability of Ku70-, Ku86- or DNA-PKcs-deficient rodent cells, in parallel with respective control cells, in response to high dose-rate (HDR) and low dose-rate (LDR) γ-ray radiation (~0.9 and ~1 mGy/min, respectively). Control cells and murine embryonic fibroblasts (MEF) from a severe combined immunodeficiency (scid) mouse, which is DNA-PKcs-deficient, showed higher cell survival after LDR irradiation than after HDR irradiation at the same dose. On the other hand, MEF from Ku70^−/− mice exhibited lower clonogenic cell survival after LDR irradiation than after HDR irradiation. XR-V15B and xrs-5 cells, which are Ku86-deficient, exhibited mostly identical clonogenic cell survival after LDR and HDR irradiation. Thus, the dose-rate effect in terms of clonogenic cell survival is diminished or even inversed in Ku-deficient rodent cells. These observations indicate the involvement of Ku in the dose-rate effect.     

Biological effects of low-dose γ-ray irradiation on chromosomes and DNA of Drosophila melanogaster

While the damage to chromosomes and genes induced by high-dose radiation (HDR) has been well researched in many organisms, the effects of low-dose radiation (LDR), defined as a radiation dose of ≤100 mSv, are still being debated. Recent research has suggested that the biological effects of LDR differ from those observed in HDR. To detect the effect of LDR on genes, we selected a gene of Drosophila melanogaster, known as the multiple wing hair (mwh) gene. The hatched heterozygous larvae with genotype mwh/+ were irradiated by γ-rays of a ⁶⁰Co source. After eclosion, the wing hairs of the heterozygous flies were observed. The area of only one or two mwh cells (small spot) and that of more than three mwh cells (large spot) were counted. The ratio of the two kinds of spots were compared between groups irradiated by different doses including a non-irradiated control group. For the small spot in females, the eruption frequency increased in the groups irradiated with 20–75 mGy, indicating hypersensitivity (HRS) to LDR, while in the groups irradiated with 200 and 300 mGy, the frequency decreased, indicating induced radioresistance (IRR), while in males, 50 and 100 mGy conferred HRS and 75 and 200 mGy conferred IRR. For the large spot in females, 75 mGy conferred HRS and 100–800 mGy conferred IRR. In conclusion, HRS and IRR to LDR was found in Drosophila wing cells by delimiting the dose of γ-rays finely, except in the male large spot.     

甲基汞、电离辐射对小鼠胸腺DNA合成及适应性反应的影响

为了解环境理化因子作用对机体产生的生物效应,采用＾３Ｈ－ＴｄＲ掺入法研究了甲基汞和不同剂量的电离辐射对小鼠胸腺ＤＮＡ合成及适应性反应的影响。结果表明：甲基汞可以抑制胸腺细胞ＤＮＡ合成;低剂量的电离辐射（０．０７５Ｇｙ）对胸腺ＤＮＡ合成具有一定刺激作用,＾３Ｈ－ＴｄＲ掺入量明显高于对照组;而高剂量的电离辐射（２Ｇｙ）对胸腺细胞ＤＮＡ合成有抑制作用;经低剂量电离辐射预处理后再进行甲基汞染毒时比单独用甲     

Low dose radiation increased the therapeutic efficacy of cyclophosphamide on S(180) sarcoma bearing mice

We examined whether low dose radiation (LDR) exposure (75 mGy) could increase the therapeutic efficacy of cyclophosphamide (CTX) by comparing the effects of tumor suppression, tumor cell apoptosis, cell cycle and proliferation of bone marrow in vivo. Kunming mice implanted with S(180) sarcoma cells were given 75 mGy whole body gamma-ray radiation exposure and CTX (300 mg/kg) by intraperitoneal injection 36 hours after LDR. Proliferation of bone marrow and tumor cells was analyzed by flow cytometry. Cytochrome c leakage from the tumor was measured by Western-blot. We discovered that tumor growth was significantly reduced in the group exposed to CTX add to LDR. The apoptosis of tumor cells increased significantly after LDR. The tumor cells were arrested in G(1) phase in the groups treated with CTX and CTX + LDR, but cell cycle was more significantly arrested in mice exposed to LDR followed by CTX than in mice exposed only to LDR or CTX chemotherapy. Concentration of bone marrow cells and proliferation index in CTX + LDR mice were higher than those in the untreated mice. LDR or CTX + LDR could induce greater cytochrome c levels and caspase-3 activity in tumors. These results suggest that low dose radiation can enhance the anti-tumor effect of the chemotherapy agent CTX markedly. Furthermore, LDR significantly protects hematopoetic function of the bone marrow, which is of practical significance on adjuvant chemotherapy.     

Evolving perspectives on the concept of dose in radiobiology and radiation protection

Since the discovery of the x ray more than 90 y ago, the biological effects of radiation have been a subject of intensive and continuing study. At the outset, such study was severely hampered by the lack of a suitable method of dosimetry. More than a quarter of a century elapsed before the introduction of a quantitative system for measuring exposure, and another quarter of a century elapsed before the introduction of quantitative units of absorbed dose. In the meantime, the effects of a given dose had long since been found to depend on its distribution in space and time; that is, on the precise spatial and temporal patterns of energy deposition within absorbing tissues and cells. Study of the biological effects of radiation thus led to elaboration of the concept of dose, to take into account relevant microdosimetric parameters. Advances in ongoing research on the molecular mechanisms of radiation effects can be expected to result in further evolution of such coNcepts.     

Low-dose radiation induces adaptive response in normal cells, but not in tumor cells: in vitro and in vivo studies

Biological effects of low-dose radiation (LDR) are distinguishable from those of high-dose radiation. Hormetic and adaptive responses are such two examples. However, whether adaptive response could be induced in tumor cells by LDR, especially under in vivo condition, remains elusive, and was systemically investigated in the present study. Four tumor cell lines: two human leukemia cell lines (erythroleukemia cell line K562, and acute promyelocytic leukemia cell line HL60), and two human solid tumor cell lines (lung carcinoma cell line NCI-H446 and glioma cell line U251), along with one normal cell line (human fibroblast cells, MRC-5), were irradiated with LDR at 75 mGy of X-rays as D1 and then 4 Gy of X-rays as D2 (i.e.: D1 + D2) or only 4 Gy of X-rays (D2 alone). Three tumor-bearing animal models were also used to further define whether LDR induces adaptive response in tumor cells in vivo. Adaptive response was observed only in normal cell line, but not in four tumor cell lines, in response to LDR, showing a resistance to subsequent D2-induced cell growth inhibition. Three tumor-bearing mouse models with U251, NCI-H446 or S180 tumor cells were used to confirm that pre-exposure of tumor-bearing mice to D1 did not induce the resistance of tumor cells in vivo to D2-induced tumor growth inhibition. Furthermore, a higher apoptotic effect, along with higher expression of apoptosis-related genes P53 and Bax and lower expression of anti-apoptosis gene Bcl-2, was found in tumor cells of the tumor-bearing mice exposed to D1 + D2 than those in the tumor cells of the tumor-bearing mice exposed to D2 alone. These results suggest that LDR does not induce adaptive response in the tumor cells under both in vitro and in vivo conditions, which is a very important, clinic-relevant phenomenon.