重离子12C对60Coγ射线诱发人染色体畸变效应的比较研究

目的 重离子和高剂量率^60Coγ射线照射离体人血建立染色体畸变的剂量-效应曲线；比较重离子^12C照射与^60Coγ射线照射诱发染色体畸变的相对生物效能。方法 重离子^12和^60Coγ射线照射离体人血，吸收剂量率为3Gy/min，吸收剂量为1．0～8．0Gy。主要记录染色体型畸变的非稳定性畸变，对双着丝粒体和着丝粒环做曲线拟合，并检验回归系数的显著性和曲线的拟合度。结果 重离子^12C和^60Coγ射线照射离体血诱发的染色体畸变(双 环)，在0—8Gy范围内，呈良好的剂量一效应关系。^12C离子诱发染色体畸变的RBE值是不恒定的，它随吸收剂量增加而减少，在0．3—8．0Gy范围内，RBE值(Dr/Dc)从2．62到1．00，平均1．58。结论 ^12C离子对^60Coγ射线照射诱发染色体畸变，在照射剂量较低时，有较高的生物效应。     

褐藻糖胶对60Co-γ 射线照射小鼠造血系统的辐射防护作用研究简

目的观察褐藻糖胶对^60Co-γ射线照射小鼠体内造血系统的辐射防护作用。方法以BALB／c小鼠进行体内照射,一次性全身照射前腹腔注射给予褐藻糖胶3d,测定脾指数、脾脏内部结构以及内源性脾结节数（7．5Gy）、骨髓有核细胞计数（6．0Gy）、外周血象（5．5Gy）。结果小鼠体内造血系统实验显示7．5Gy^60Co-γ照射后,各给药照射组的脾指数及内源性脾结节数明显较对照组增多,中剂量照射组的脾脏大小以及脾脏内部组织结构均比对照组有显著的差别;6．0Gy^60Co-γ照射后,小鼠骨髓有核细胞数较正常对照组相比差异非常显著（P〈0．01）,各给药照射组与照射对照组比较,均高于照射对照组（P〈0．05或P〈0．01）：5．5Gy^60Co-γ照射后30d,小鼠外周血象测定中各给药照射组白细胞数明显高于对照组（P〈0．01）,而外周血红细胞、血红蛋白和血小板无明显影响。结论褐藻糖胶对^60Co-γ射线照射引起的小鼠造血系统损伤有保护作用。     

不同剂量γ射线照射后胎儿骨髓CD34+造血干细胞死亡规律

目的 探讨不同剂量γ射线照射后胎儿骨髓CD34^ 造血干细胞的死亡规律。方法 以流式细胞术PE－CD34^ ／FITC－AmnexinV/7AAD三色荧光法、多参数分析了受不同剂量γ射线照射后,不同时间点的胎儿骨髓CD34^ 造血干细胞凋亡、坏死和存活的时效和量效变化特点。结果 受大剂量率γ射线1次5Gy和8Gy照射后,和骨髓CD34^ 造血干细胞的死亡是在照射后为期1周的连续性死亡,既有凋亡又有坏死,但是以凋亡为主;受大剂量率γ射线1次10Gy和12Gy照射后,胎儿骨髓CD34^ 造血干细胞则在受照后当天即大量坏死,在持续1周内全部死亡。结论 受大剂量率γ射线1次照射后,造血干细胞在1周内发生了增殖期死亡而连续性空出所占据的龛位。     

X射线全身照射诱导小鼠脾细胞LAMP-1 表达的时程变化

目的观察X射线全身照射对小鼠脾细胞LAMP-1表达的影响。方法采用流式细胞术检测0．075和2Gy X照射后不同时间（0、2、4、8、16、24和48h）以及用Con A刺激4h后，脾细胞表面表达LAMP-1的阳性细胞数。结果脾细胞表面的LAMP-1在2Gy X射线全身照射后8、16和24h表达明显下降；0．075Gy X射线全身照射后2h显著升高，而48h又下降到低于对照的水平。0．075和2Gy X射线全身照射后再加用Con A（10μg／μl）刺激4h，LAMP-1的表达均增强；但是此时2Gy的效应比0．075Gy更明显。结论LAMP-1参与电离辐射作用下免疫信号的传导，高剂量X射线抑制它的表达，而低剂量X射线在早期对其表达有促进作用，与体内免疫细胞的活性密切相关。Con A促进免疫细胞表面LAMP-1的表达。     

γ射线对培养的兔血管平滑肌细胞的抑制作用

目的 观察体外培养的兔动脉平滑肌细胞(SMCs）对7射线照射的剂量效应关系，探讨电离辐射抑制SMCs增殖的细胞生物学机理。方法 静止期SMCs分别给予γ射线2．5，5，10，20及30Gy一次性照射后继续培养4，24或72h。以^3H—TdR掺入法、流式细胞术分析、微核实验和电镜观察γ射线对SMCs的DNA合成、增殖周期和损伤的影响。结果 在2．5Gy以上剂量γ射线一次性照射时，SMCs增殖明显抑制，细胞G0／G1期阻滞，均呈剂量依赖性。2．5Gy以下剂量γ射线照射后24h左右可见细胞凋亡增加，2．5Gy以上剂量7射线照射可使SMCs发生坏死。结论 电离辐射能抑制SMCs增殖，使细胞产生G0／G1期阻滞，并呈剂量依赖关系。SMCs死亡方式与受照射剂量有关。     

~(60)Coγ射线和14MeV中子的单次和分割照射对小鼠精原干细胞的效应

目的 :电离辐射对男性生殖腺的远期效应可能是引起精源干细胞损伤。因此 ,研究了γ射线和中子的单次和分割照射对小鼠精原干细胞的相对生物效应 (RBE)。方法 :选 8～ 12周龄雄性 NMRI小鼠 ,每一剂量和每一时间组用 4只 ,2 0只作对照 ,用 6 0 Coγ射线 10 c Gy～ 15 Gy(剂量率 5 0 c Gy/ min)或 14Me V中子 10 c Gy～ 7Gy(剂量率 10～2 0 c Gy/ min)单次或分隔两个等分间隔 2 4h照射小鼠体后部位。每只小鼠处死后取出睾丸 ,睾丸细胞 DNA用 5 μmol/ L4′,6 -二脒基 - 2 -苯基吲哚盐酸 (DAPI)染色 ,用 PAS 流式细胞仪测得典型的睾…     

低剂量辐射对小鼠睾丸生精细胞中细胞色素c和caspase-3表达的影响

目的 研究低剂量电离辐射对小鼠睾丸生精细胞细胞色素c（Cytc）和caspase-3蛋白表达的影响。方法 采用免疫组化法（SABC法），观察低剂量X射线照射后，小鼠睾丸各类生精细胞Cytc和caspase-3表达的剂量与时程效应关系。结果 0、0.025、0．05、0．075、0．1和0.2Gy照射后12h，小鼠睾丸各类生精细胞不同程度表达Cyt c和caspase-3，以精原细胞和精母细胞表达为主，精于细胞和精于则表达相对较少，而且，随着剂量的增加，表达也增多。0．075Gy照射后。两种蛋白的表达开始随时间推移而增强，12h达到峰值，然后下降，但仍高于正常组。结论低剂量电离辐射诱导小鼠睾丸生精细胞Cytc和caspase-3蛋白的表达具有一定的剂量和时程效应规律性。     

扇贝多肽对(60)Co γ射线诱导的胸腺细胞凋亡的影响

目的评价扇贝多肽对^60Coγ射线诱导的胸腺细胞凋亡的作用。方法昆明小鼠胸腺细胞^60Coγ射线3Gy照射，吸收剂量率0．6Gy／min。实验分空白对照组，模型组，扇贝多肽不同浓度(0．5，0．2．5和0．125mg／m1)预处理为实验组，通过受照细胞形态、生化、DNA和相关酶变化来进行评价。结果经扇贝多肽预处理的实验组细胞有较低的细胞毒性，细胞凋亡受到抑制，细胞脂质过氧化(MDA)水平有所降低而超氧化物歧化酶(SOD)活性可以维持在正常水平。结论扇贝多肽对^60Coγ射线照射所致昆明小鼠胸腺细胞的损伤有保护作用。     

中子辐射后骨髓造血功能损伤以及IL-11受体的表达变化

目的 探讨IL-11受体在中于照射骨髓造血细胞损伤后的变化规律及其意义。方法 100只雄性BALB／c小鼠经2．5和4．0Gy中子全身照射，于照射后6h，1、2、3、5、7、14和28d分批活杀，应用光镜和电镜观察骨髓病理变化；流式细胞术和DNA凝胶电泳检测骨髓细胞凋亡；免疫组化和图像分析定量检测IL-11Rα及gp130的表达。结果 2．5Gy中子照射后3d内，小鼠骨髓造血细胞见凋亡与坏死，数量进行性减少；至照射5d后逐渐恢复，28d恢复至正常。4．0Gy中子照射，骨髓损伤更严重，未见恢复。2．5Gy中子照射后1d内，IL-11Rα在造血细胞膜及胞浆略有增加，2～7d减少，14d后逐渐恢复；而gp130于照射后7d内在造血细胞膜及胞浆减少，14d后逐渐恢复。4．0Gy照射后2d内，IL-11Rα和gp130均进行性减少，较2．5Gy减少更为明显。结论 IL-11Rα及gp130表达在中于照射后骨髓损伤期减少，而于恢复期逐渐恢复，参与了骨髓辐射损伤后造血功能重建的病理生理过程。     

低剂量电离辐射诱导小鼠胸腺细胞凋亡及细胞周期进程适应性反应的时间效应

目的：观察低剂量辐射诱导胸腺细胞凋亡及细胞周期进程适应性反应的基本规律。方法：实验用X射线照射昆明雄性小鼠,其诱导剂量（D1）及其后攻击剂量（D2）分别是75mGy和1．5Gy。D1和D2间隔时间分别是3、6、12、24和60h。通过流式细胞仪检测胸腺细胞凋亡和细胞周期进程的变化。结果：当D1和D2间隔3、6和12h ,D1 D2组胸腺细胞凋亡百发数明显低于D2组（P＜0．05）,G0／G1和G2＋M期细胞百分数也不同程度地低于D2组,而S期是分数却明显高于D2组（P＜0．0．5或P＜0．01）。结论上述结果指出,D1在75mGy,吸收剂量率为12．5mGy／min,D2在1．5Gy,吸收剂量率为0．287Gy／min;D1和D2间隔3－12h,可在全身照射条件下诱导小鼠胸腺细胞凋亡和细胞周期进程的适应性反应。     

Threshold effect for teratogenic risk of radiation depends on dose-rate and p53-dependent apoptosis

PURPOSE: To obtain evidence that the p53 gene is indispensable for reduction of high teratogenic risk of radiation at a high dose-rate to zero risk by lowering the dose-rate. MATERIALS AND METHODS: Wild-type p53(+/+), heterozygous p53(+/-) and null p53(-/-) mice were exposed to gamma-rays at high or low dose-rates during days 9.5-10.5 of gestation. The incidence of malformations and prenatal deaths was studied. Frequencies of cells dying by apoptosis were measured during or after protracted irradiation. RESULTS: After irradiation with 2 Gy, the frequency of apoptotic cells increased to 20% for p53(+/+) mice and did not increase at all for p53(-/-) mice. For p53(+/+) mice, 2 Gy y-rays induced 70% malformations when given at 1.06 Gy/min, but no malformations above the control when given at 1.2 mGy/min. In contrast, after irradiation of p53(-/-) foetuses with 2 Gy at 1.2mGy/min, the incidence of malformations increased 12% above control levels. CONCLUSION: Foetal irradiation with 2 Gy at 1.2 mGy/min was not teratogenic for p53(+/+) mice but teratogenic for p53(-/-) mice. This indicates that the p53 gene is indispensable for a threshold effect in the risk of radiation at low doses or dose-rates.     

电离辐射对小鼠脾淋巴细胞IL-10表达的影响

目的 观察75mGy、2GyX射线全身照射对小鼠脾淋巴细胞中IL－10的影响。方法 采用Northern blot检测IL－10转录水平的变化，并同时通过流式细胞术检测其蛋白合成的变化。结果 ①蛋白合成结果表明，75mGy X射线全身照射后脾淋巴细胞IL－10合成在照后2h开始即呈时间依赖性降低，至48h仍无恢复迹象（P＜0．01），而2Gy照射后则出现IL－10合成升高，于照射后8h达到峰值（P＜0．05）。②Northern blot结果表明，75mGy照射后脾细胞IL－10 mRNA转录水平从照后1h即降低，并维持较低水平一直到48h开始恢复，达到假照射组的88．35％；2GyX射线全身照射后早期mRNA水平即有所升高，2h达到假照组的134．06％，4h略有下降，随后逐渐恢复至假照射组水平。结论 不同剂量X射线全身照射可引起不同的辐射效应，IL－10在其中起着重要的作用。     

电离辐射对小鼠胸腺Th17细胞相关细胞因子的影响

目的 通过研究电离辐射对小鼠胸腺Th17细胞相关细胞因子的影响,探讨高、低剂量辐射诱导不同的免疫效应中Th17细胞功能。方法 将健康ICR小鼠按随机数字表法分为健康对照组、低剂量照射组(0.05、0.075 Gy)和高剂量照射组(0.5、1.0、2.0、4.0 Gy)探讨剂量-效应关系,用X射线深部治疗机进行不同剂量的全身照射,于照射后24 h处死。同时,探讨时间-效应关系,即分为健康对照组、低剂量照射组(0.075 Gy)和高剂量照射组(2.0 Gy),于照射后12、24、48 h处死,取胸腺组织制备成组织匀浆,ELISA法检测小鼠胸腺细胞中白介素-17a(IL-17a)与白介素-21(IL-21)的浓度。结果 在时间-效应结果中,与健康对照组相比,0.075 Gy照射组胸腺细胞IL-17a和IL-21分泌量呈下降趋势,其分泌量于48 h降到最低(t=3.85、4.73,P<0.05);而2.0 Gy照射组均呈大幅度上升趋势,其分泌量在48 h达到最高(t=-6.74、-6.19,P<0.05);在剂量-效应结果中,与健康对照组相比,较低剂量照射组胸腺细胞IL-17a与IL-21分泌量下降,在0.05 Gy最低(t=8.39、16.45,P<0.05);较高剂量照射组胸腺细胞的分泌量上升,在4.0 Gy时升至最高(t=-15.60、-18.62,P<0.05)。结论 高剂量辐射可以诱导小鼠胸腺细胞IL-17a与IL-21分泌量的增加,而低剂量辐射使其下降,表明Th17细胞相关的细胞因子在低剂量辐射诱导的免疫功能增强效应和高剂量辐射诱导免疫抑制效应中起着重要的作用。     

Radiation response of apoptosis in C57BL/6N mouse spleen after whole-body irradiation

Purpose : Primary conditioning low dose irradiation suppresses the molecular responses against secondary challenge high dose irradiation; this phenomenon has been termed the radioadaptive response. The mechanism of the radioadaptive response is not yet clear. This study was undertaken to elucidate the radiation response of apoptosis in mouse spleen after whole-body irradiation. Materials and methods : The induction of apoptosis was analysed in the spleens of C57BL/6N mice after chronic irradiation with γ-rays at 1.5 Gy (0.001 Gy/min for 25 h) followed by challenge irradiation with X-rays at 3.0Gy (1 Gy/min). Results : Accumulation of p53 and Bax, and the induction of apoptosis were observed dose-dependently in mouse spleen 12 h after acute irradiation at a high dose-rate. However, it was found that there was significant suppression of the accumulation of p53 and Bax, and induction of apoptosis 12 h after challenge irradiation at 3.0Gy at a high dose-rate following chronic preirradiation at 1.5Gy at a low dose-rate. In addition, the combination of pre-irradiation at 1.5Gy at a high dose-rate and challenge irradiation at 3.0Gy at a high dose-rate could not suppress the accumulation of p53 and Bax or the induction of apoptosis. Conclusions : Chronic pre-irradiation at a low dose-rate suppressed Bax-mediated apoptosis. These findings suggest that the radioadaptive response in mouse spleen may be due to a suppression of p53-mediated apoptosis.     

Radiation response of apoptosis in C57BL/6N mouse spleen after whole-body irradiation

PURPOSE: Primary conditioning low dose irradiation suppresses the molecular responses against secondary challenge high dose irradiation; this phenomenon has been termed the radioadaptive response. The mechanism of the radioadaptive response is not yet clear. This study was undertaken to elucidate the radiation response of apoptosis in mouse spleen after whole-body irradiation. MATERIALS AND METHODS: The induction of apoptosis was analysed in the spleens of C57BL/6N mice after chronic irradiation with gamma-rays at 1.5 Gy (0.001 Gy/min for 25 h) followed by challenge irradiation with X-rays at 3.0Gy (1 Gy/min). RESULTS: Accumulation of p53 and Bax, and the induction of apoptosis were observed dose-dependently in mouse spleen 12 h after acute irradiation at a high dose-rate. However, it was found that there was significant suppression of the accumulation of p53 and Bax, and induction of apoptosis 12 h after challenge irradiation at 3.0Gy at a high dose-rate following chronic preirradiation at 1.5Gy at a low dose-rate. In addition, the combination of pre-irradiation at 1.5Gy at a high dose-rate and challenge irradiation at 3.0Gy at a high dose-rate could not suppress the accumulation of p53 and Bax or the induction of apoptosis. CONCLUSIONS: Chronic pre-irradiation at a low dose-rate suppressed Bax-mediated apoptosis. These findings suggest that the radioadaptive response in mouse spleen may be due to a suppression of p53-mediated apoptosis.     

Chromosomal radiosensitivity in secondary-progressive multiple sclerosis patients

PURPOSE: To investigate chromosomal radiosensitivity of secondary progressive (SP) multiple sclerosis (MS) patients in comparison to a group of healthy individuals. MATERIAL AND METHODS: Chromosomal radiosensitivity was assessed in vitro with the G2 assay and the G0-micronucleus (MN) assay. For the G2 assay phytohaemagglutinin (PHA) stimulated blood cultures were irradiated with a dose of 0.4 Gy 60Co gamma rays in the G2 phase of the cell cycle. For the MN assay unstimulated diluted blood samples were exposed to 3.5 Gy 60Co gamma rays delivered at a high dose-rate (HDR = 1 Gy/min) or low dose-rate (LDR = 4 mGy/min). RESULTS: No significant differences in the number of chromatid breaks were observed between MS patients and healthy individuals. With the G0-MN assay a higher spontaneous MN yield was found in MS patients. At HDR irradiation no significant differences were shown, while at LDR irradiation, MS patients were found less sensitive than healthy controls. The dose-rate sparing index was higher for MS patients, pointing to a better repair capacity. CONCLUSIONS: MS patients are not characterised by an enhanced in vitro chromosomal radiosensitivity. The radioresistant response, which was only observed with the MN assay after LDR irradiation, may point to an adaptive response induced by in vivo oxidative stress in SPMS patients.     

Alterations of immune functions induced by 12C6+ ion irradiation in mice

PURPOSE: To estimate the biological risks to the immune system of the type of space radiation, 12C6+, encountered by cosmonauts during long-term travel in space. MATERIALS AND METHODS: The Kun-Ming strain mice were whole-body irradiated by 12C6+ ion with 0, 0.01, 0.05, 0.075, 0.2, 0.3, 0.5, 0.75, 1 or 2 Gy, at a dose rate of 1 Gy/min. At 35 days after irradiation, the thymus and spleen weights were measured, the natural killer (NK) cells activity of spleen was determined by 3-(4, 5-dimethylthiazol-2-yl)- 2, 5-diphenyl tetrazolium bromide (MTT), and the interferon-gamma (IFN-gamma) levels in serum and thymus were detected with enzyme-linked immunosorbent assays (ELISA). RESULTS: The results showed that the thymus weight, IFN-gamma levels in serum and the activity of splenic NK-cells had significantly increased at a dose of 0.05 Gy. With further dose increase, the weight of spleen continued to increase but the weight of thymus, IFN-gamma level and NK-cells activity declined. CONCLUSIONS: These results suggest that the dose of 0.05 Gy irradiation has a stimulatory effect on mouse immunity; this effect declined with increasing dose.     

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.     

低剂量辐射诱导免疫适应性反应的最佳时间

本实验观察了低剂量Ｘ射线全身单次照射诱导昆明小鼠免疫适应性反应的最佳时间．证实当预照射剂量（Ｄ＿１剂量）为７５ｍＧｙ．剂量率１２．５ｍＧｙ／ｍｉｎ，损伤剂量（Ｄ＿２剂量）为１．５Ｇｙ，剂量率０．３３Ｇｙ／ｍｉｎ，Ｄ＿１与Ｄ＿２间隔６ｈ可诱导脾细胞对脂多糖反应的适应性反应，Ｄ＿１与Ｄ＿２间隔１２ｈ可诱导胸腺细胞自发增殖及脾细胞对ＣｏｎＡ及脂多糖反应的适应性反应．以上结果表明，当Ｄ＿２为１．５Ｇｙ时。７５ｍＧｙ诱导上述免疫适应性反应的最佳时间间隔为６ｈ及１２ｈ．     

Alterations of immune functions induced by 12C6+ ion irradiation in mice

Purpose:?To estimate the biological risks to the immune system of the type of space radiation, 12C6+, encountered by cosmonauts during long-term travel in space.

Materials and methods:?The Kun-Ming strain mice were whole-body irradiated by 12C6+ ion with 0, 0.01, 0.05, 0.075, 0.2, 0.3, 0.5, 0.75, 1 or 2 Gy, at a dose rate of 1 Gy/min. At 35 days after irradiation, the thymus and spleen weights were measured, the natural killer (NK) cells activity of spleen was determined by 3-(4, 5-dimethylthiazol-2-yl)- 2, 5-diphenyl tetrazolium bromide (MTT), and the interferon-γ (IFN-γ) levels in serum and thymus were detected with enzyme-linked immunosorbent assays (ELISA).

Results:?The results showed that the thymus weight, IFN-γ levels in serum and the activity of splenic NK-cells had significantly increased at a dose of 0.05 Gy. With further dose increase, the weight of spleen continued to increase but the weight of thymus, IFN-γ level and NK-cells activity declined.

Conclusions:?These results suggest that the dose of 0.05 Gy irradiation has a stimulatory effect on mouse immunity; this effect declined with increasing dose.