Mechanism of cytogenetic adaptive response induced by low dose radiation

Cytogenetic observation on human lymphocytes indicated that pre-exposure of 10, 50 and 75 mGy X-rays could induced the adaptive response. Experimental results with different temperature treatment showed that the adaptive response induced by low dose radiation could be enhanced by 41 degrees C and 43 degrees C, but inhibited by 4 degrees C in addition the treatment by 41 degrees C for one hour could also cause the adaptive response as did low dose radiation. Results showed that adaptive response induced by low dose radiation (10 or 50 mGy X-rays) could be eliminated by the protein synthesis inhibitor, implying that the adaptive response is related with the metabolism of cells, especially with the production of certain protective proteins.     

Adaptive response of thymocyte apoptosis and cell cycle progression induced by low dose X-ray irradiation in mice

The dose-effect of adaptive response of thymocyte apoptosis and cell cycle progression induced by whole-body X-ray irradiation (WBI) was studied in male Kunming mice. The inductive doses (D1) were 25, 50, 75, 100 or 200 mGy 6 h before the challenging doses (D2) of 1.0, 1.5 or 2.0 Gy. The changes in the percentages of the thymocyte apoptotic bodies (TAB) and the cells in different phases of cell cycle were measured with flow cytometry. The percentages of TAB decreased, the arrests of G1 and G2 + M phases diminished, and the cells of DNA synthesis of S phase increased when the D1 + D2 groups was compared with the D2 groups. When D1 was 200 mGy, the adaptive response of thymocyte apoptosis and cell cycle progression were no longer induced by low dose radiation (LDR). In addition, the extracellular fluid from the splenocytes were cultured with Con A for 48 h in vitro 24 h after 75 mGy WBI was placed in the murine thymocyte suspension from mice irradiated with 2.0 Gy WBI and co-incubated. The thymocyte apoptosis decreased. Especially, noteworthy was that the percentages of TAB after the incubation for 72 h were significantly lower than those in 2.0 Gy irradiated thymocytes (P < 0.05). These results indicate that when the mice were irradiated with 25-100 mGy (D1, 12.5 mGy/min) 6 h before 1.0-2.0 Gy (D2, 0.287 Gy/min) exposure, an adaptive response of thymocyte apoptosis and cell cycle progression may be induced under the condition of WBI, and LDR (75 mGy) may change the microenvironment of immune cells and decrease the thymocyte apoptosis.     

低剂量X线照射诱导小鼠胸腺细胞凋亡适应性反应的相关凋亡基因p53、Bcl-2和Bax蛋白表达

目的：探讨低剂量辐射诱导胸腺细胞凋亡适应性反应的相关基因蛋白调控机制。方法：用X射线全身照射Kunming系雄性小鼠,其诱导剂量（D1）为25、50、75、100和200 mGy（剂量率12.5 mGy•min^-1）,攻击剂量（D2）为1.5 Gy（剂量率287 mGy•min^-1）,D1和D2间隔6 h。通过流式细胞仪检测胸腺细胞凋亡相关基因p53、Bcl-2和Bax蛋白表达水平。 结果：D2组与假照射组比较,其胸腺细胞Bcl-2蛋白阳性百分率明显降低（P<0.05）,Bax蛋白明显增加（P<0.05）,而Bcl-2/Bax比值非常明显降低（P<0.001）;p53蛋白非常明显增加（P<0.001）。D1+D2组与D2组比较,D1在25～75 mGy时,Bcl-2蛋白阳性百分率不同程度增加,Bax蛋白不同程度降低,而Bcl-2/Bax比值非常明显增高（P<0.01）;p53蛋白明显降低（P<0.001或P<0.05）。 结论：在25～75 mGy低剂量辐射诱导小鼠胸腺细胞凋亡的适应性反应中,其相关凋亡基因蛋白Bcl-2表达增加,Bax降低,Bcl-2/Bax比值增高,p53降低,导致凋亡的胸腺细胞减少。     

Adaptive response of thymocyte apoptosis induced by X-irradiation with 75 mGy

目的：本研究观察胸腺细胞凋亡小体（TAB）以评价低剂量辐射诱导的胸腺细胞凋亡的适应性反应。方法：实验用X射线全身照射Kunmin雄性小鼠，诱导剂量75mGy（D1），攻击剂量1．5或2．0Gy（D2），D1和D2间隔6h，D2照后20h检测TAB百分数。结果：D1+D2组TAB百分数明显低于D2组（P＜0．05）。此外，将75mGy照射的脾细胞外液加入2Gy照射的胸腺细胞悬液中，在培养72h明显低于2Gy照射组（P<0．05）。结论：低剂量辐射（75mGy）可改变免疫细胞的外环境，降低其凋亡，并且可诱导其后大剂量（1．5或2．Gy）照射的小鼠胸腺细胞凋亡的适应性反应。     

低剂量辐射诱导遗传损伤适应性反应的时间效应

利用小鼠生殖细胞为实验材料，观察低剂量辐射诱导遗传损伤适应性反应的时间效应。结果表明：以５０ｍＧｙＸ射线为Ｄ１剂量，然后在不同间隔时间照射Ｄ２（１．５ＧｙＸ射线），其间隔时间在２４ｈ内的不同时间照射Ｄ２，精原细胞和初级精母细胞染色体畸变率下降，出现明显的适应性反应，以３～６ｈ为最佳；以５０ｍＧｙ×４的多次照射和慢性小剂量６０Ｃｏγ射线照射（累积剂量为１．１０Ｇｙ）为Ｄ１剂量，在照射后４０ｄ仍可出现适应性反应现象。说明，单次急性照射的适应性反应持续时间较短；而多次照射和慢性照射适应性反应持续时间较长。     

辐射诱导小鼠免疫细胞蛋白质表达变化及酪氨酸磷酸化

目的：为进一步了解低剂量辐射对免疫细胞早期蛋白质表达及酪氨酸磷酸化的影响。方法：采用SDS-聚丙烯酰胺凝胶电泳、光密度扫描及免疫沉淀方法观察75mGyX射线全身照射对小鼠免疫细胞蛋白质表达变化及酪氨酸磷酸化的影响。结果：照射后小鼠胸腺细胞Mr=28000及Mr=43000蛋白质表达增强；脾细胞Mr=32000及Mr=43000蛋白质表达增强；三种蛋白质均发生酪氨酸磷酸化。结论：这些早期变化的蛋白质参与复杂的细胞功能调节，可能与辐射兴奋效应有关。     

低剂量电离辐射诱导免疫适应性反应的时间效应

本研究采用Ｘ线全身照射昆明系雄性小鼠模型，观察电离辐射诱导免疫适应性反应的预照射剂量（Ｄ１剂量，７５ｍＧｙ）及其后损伤性剂量（Ｄ２剂量，１．５～２．０Ｇｙ）的时间效应。结果表明，Ｄ１与Ｄ２时间间隔６～４８ｈ，Ｄ２照后１８～２４ｈ可诱导胸腺细胞自发增殖能力及脾细胞对丝裂原（ＣｏｎＡ和ＬｐＰＳ）反应性等适应性反应。     

辐射对淋巴细胞RNA、蛋白质合成的影响及其诱导的适应性反应

目的　观察电离辐射对淋巴细胞ＲＮＡ、蛋白质合成的影响及其诱导的适应性反应。方法　采用体外培养的淋巴细胞,经丝裂原ＰＨＡ刺激后,　１４Ｃ－ ＵＲ、　３Ｈ－ Ｔｙｒｏｓｉｎｅ 双标记掺入法观察０ ．５ ～８ ．０Ｇｙ　γ射线照射后,ＲＮＡ和蛋白质合成速率的变化及低剂量（Ｄ１ ＝４ ．８ｃＧｙ） 照射后相继攻击剂量（Ｄ２） 照射,淋巴细胞所表现的适应性反应。结果　体外培养的淋巴细胞随着照射剂量的增加,ＲＮＡ 和蛋白质合成速度下降,并表现出对低剂量辐射诱导的适应性反应。结论　电离辐射可致淋巴细胞ＲＮＡ、蛋白质合成速度下降,但低剂量辐射可诱导淋巴细胞的适应性反应     

低剂量辐射诱导EL-4淋巴瘤细胞凋亡及细胞周期进程适应性反应的剂量率效应

目的：观察低剂量辐射诱导EL-4淋巴瘤细胞凋亡及细胞周期进程适应性反应的剂量率效应,以揭示低剂量辐射生物效应及其诱导适应性反应的可能机制。方法：实验分D2组（攻击剂量）、D1（诱导剂量）+ D2组和假照组。用X射线照射离体EL-4淋巴瘤细胞,其D1为75 mGy（剂量率6.25~200.00 mGy•min^-1）,D2为1.5 Gy（剂量率287 mGy/min）,D1和D2间隔6 h。通过流式细胞仪检测其细胞凋亡和细胞周期进程的变化。结果：当D1剂量率为6.25~50.00 mGy,D1 + D2组细胞凋亡百分数明显低于D2组（P<0.05）G₀/G₁期细胞百分数明显低于D2组（P<0.01）,而S期细胞百分数不同程度高于D2组。结论：D1为75 mGy（剂量率6.25~50.00 mGy•min^-1）,D2为1.5 Gy（剂量率287 mGy•min^-1）、D1和D2间隔6 h,可诱导体外EL-4淋巴瘤细胞凋亡和细胞周期进程的适应性反应。     

低剂量辐射诱导EL-4淋巴瘤细胞凋亡及细胞周期进程适应性反应的时间效应

目的：研究低剂量辐射诱导EL-4淋巴瘤细胞凋亡及细胞周期进程适应性反应的时间效应，以揭示低剂量辐射生物效应及其诱导适应性反应的可能机制。方法：实验分D2组（攻击剂量）、D1（诱导剂量）+ D2组和假照组。用X射线照射离体EL-4淋巴瘤细胞，其D1为75 mGy（剂量率12.5 mGy•min^-1），D2为1.5 Gy（剂量率287 mGy•min^-1），D1和D2间隔为3~60 h。通过流式细胞仪检测其细胞凋亡和细胞周期进程的变化。结果：当D1和D2间隔为3~24 h时，D1+D2组细胞凋亡百分数明显低于D2组（P<0.05或P<0.01），G₀/G₁期细胞百分数不同程度低于D2组，而S期细胞百分数明显高于D2组（P<0.05）。结论：75 mGy（12.5 mGy•min^-1）照射后3~24 h，进行1.5 Gy（287 mGy•min^-1）照射，可诱导体外EL-4淋巴瘤细胞凋亡和细胞周期进程的适应性反应。     

低剂量X线辐射诱导胸腺细胞凋亡及细胞周期进程适应性反应的剂量率效应

目的 :观察 X线低剂量辐射诱导胸腺细胞凋亡和细胞周期进程适应性反应的剂量率效应。方法 :用 X射线照射昆明种雄性小鼠 ,其诱导剂量 ( D1 )及其后攻击剂量 ( D2 )分别是 75 m Gy和1 .5 Gy,D1 剂量率为 6.2 5、1 2 .5、2 5、5 0、1 0 0和 2 0 0 m Gy· min-1 ,D2 剂量率为 2 87m Gy· min-1 ,D1 和 D2 间隔 6h。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 剂量率为 6.2 5、1 2 .5和 2 5 m Gy,D1 + D2 组胸腺细胞凋亡百分数明显低于 D2 组 ( P<0 .0 5或 P<0 .0 1 ) ,G0 / G1 和 G2 + M期细胞百分数也不同程度地低于 D2 组 ,而 S期细胞百分数明显高于 D2 组( P<0 .0 5或 P<0 .0 1 )。结论 :低剂量 X线全身照射条件下 ,剂量率在 6.2 5～ 2 5 m Gy· min-1 ,可诱导小鼠胸腺细胞凋亡和细胞周期进程的适应性反应     

Absence of radioadaptive responses in four cell-lines in vitro as determined by colony formation assay

The purpose of this study was to investigate radioadaptive response in 4 cell-lines under identical conditions using a colony assay. First, 4 cell-lines (V79, HeLa S3, EMT6 and SCCVII) were exposed to 8 Gy at various intervals after pretreatment with an adapting dose of 50 mGy or without it. Second, V79 cells were exposed to 8 Gy at 4.5 hrs after an adapting dose of 0 to 400 mGy. Third, V79 cells were exposed to 2, 4 or 6 Gy at 6 hrs after an adapting dose of 0 or 50 mGy. In the last experiment, an adapting dose was given either immediately after cell plating or 24 hrs later. Cell survival was assessed by a standard colony assay. Adaptive response was not observed in any of the 4 lines tested. In V79 cells, no adaptive response was seen even by changing the adapting dose, challenging dose, and timing of adapting radiation after cell plating. Although radioadaptive response has been reported for the V79 cell-line, we could not reproduce the result. We also failed to demonstrate the phenomenon in the other 3 tumor cell-lines in culture.     

低剂量辐射诱导小鼠胸腺细胞DNA裂解适应性反应的剂量率效应

目的：观察低剂量辐射诱导胸腺细胞DNA裂解适应性反应的剂量率效应。方法：用X射线照射Kunming雄性小鼠,其诱导剂量（D1）及其后攻击剂量（D2）分别是75 mGy和1.5 Gy,D1剂量率为6.25、12.5、25、50、100和200 mGy•min^-1,D2剂量率为287 mGy•min^-1,D1 和D2间隔6 h。通过荧光分光光度计检测DNA裂解断片的变化。结果：D2组胸腺细胞DNA裂解率明显高于假照组（P<0.001）;当D1剂量率为6.25、12.5和25 mGy•min^-1,D1＋D2组DNA裂解率明显低于D2组（P<0.05或P<0.01）。 结论：当D1在75 mGy,剂量率为6.25～25 mGy•min^-1;D2为1.5 Gy,剂量率为287 mGy•min^-1;D1和D2间隔6 h,可在全身照射条件下诱导小鼠胸腺细胞DNA裂解的适应性反应。     

“Radiation Hormesis”中的剂量率效应

为了揭示不同剂量率Ｘ射线低剂量全身照射对低剂量辐射兴奋效应（ＲａｄｉａｔｉｏｎＨｏｒｍｅｓｉｓ）的影响，采用不同剂量率（１２．７ｍＧｙ／ｍｉｎ和０．２Ｇｙ／ｍｉｎ）对Ｂａｌｂ／ｃ小鼠进行低剂量全身照射，研究了低剂量辐射兴奋效应中的剂量率效应。结果表明：采用不同剂量率Ｘ射线照射同一剂量时，所引起的生物效应不同。剂量率为１２．７ｍＧｙ／ｍｉｎ时，脾细胞３Ｈ－ＴｄＲ参入量对ＣｏｎＡ的反应性明显增强，尤其以７６．７ｍＧｙ和１０５．５ｍＧｙ照射组最为显著（Ｐ＜０．０１），表现出明显的辐射免疫兴奋效应。而剂量率为０．２Ｇｙ／ｍｉｎ时，在１０５．５ｍＧｙ以内，脾细胞３Ｈ－ＴｄＲ参入量对ＣｏｎＡ的反应性无明显变化。该结果提示：高剂量率低剂量全身照射不能引起低剂量辐射兴奋效应。     

Time-effect of adaptive response of mouse thymocyte apoptosis and cell cycle progression induced by low dose radiation

目的 :观察低剂量辐射 (LDR)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 :用 X射线照射昆明系雄性小鼠 ,其诱导剂量 (D1)及其后攻击剂量 (D2 )分别是 75m Gy和 1.5Gy。D1和 D2 间隔时间分别是 3、6、12、2 4和 6 0 h。D2 照射后 18h胸腺细胞培养 4、2 0和 4 4 h用流式细胞仪检测胸腺细胞凋亡小体 (TAB)和细胞周期进程的变化。结果 :当 D1和 D2 间隔 3、6和 12 h,在 D2 照射后胸腺细胞培养 4和 2 0 h,D1+ D2 组 TAB百分数明显低于 D2 组 (P<0 .0 5) ,G0 / G1和 G2 + M期细胞百分数也不同程度地低于 D2 组 ,而 S期细胞百分数却明显高于 D2 组 (P<0 .0 5或 P<0 .0 1)。结论 :D1和D2 分别是 75m Gy(剂量率 ,12 .5m Gy/ min)和 1.5Gy(剂量率 ,0 .2 87Gy/ min) ,D1和 D2 间隔 3～ 12 h,在小鼠全身照射后其胸腺细胞培养 4和 2 0 h可诱导细胞凋亡和细胞周期进程的适应性反应。     

低剂量辐射对人骨髓间充质干细胞造血生长因子表达量的影响

目的：探讨低剂量辐射（LDR）对人骨髓间充质干细胞（BM-MSC）的兴奋性效应及其分子机制。方法： 应用体外传代培养的P4和P5 BM-MSC,采用X射线照射,分为50、75和100 mGy 3个照射剂量组,剂量率为12.5 mGy•min^-1, 每组细胞设对应假照组,采用ELISA方法检测LDR后BM-MSC细胞因子表达量的变化。结果：与同一时间假照组比较,50、75和100 mGy X射线照射人BM-MSC后,在培养24和48 h时干细胞因子（SCF）分泌量均有升高趋势,仅75 mGy照射后48 h时SCF分泌量明显升高,与同一时间假照组比较差异有显著性（P<0.05）; 50和75 mGy照射组在24和48 h,100 mGy照射组在24 h时IL-6分泌量明显升高,与同一时间假照组比较差异有显著性（P<0.05）;50、75和100 mGy照射BM-MSC后,与同一时间假照组比较,除50 mGy 照射后 72 h外,M-SCF分泌量在照射后在24、48和72 h均明显升高（P<0.05）,以75 mGy照射后72 h升高最明显。 结论： LDR对BM-MSC有兴奋效应,表现为细胞生长加速,同时在一定时间内可以使造血生长因子表达量增多。     

低剂量电离辐射对免疫器官CuZn－SOD和Se－GSH－Px活性的影响

本研究观察低剂量Ｘ射线照射后，离体和在体大鼠胸腺和脾细胞ＣｕＺｎ一ＳＯＤ和Ｓｅ一ＧＳＨ一Ｐｘ活性的变化。结果表明，离体脾细胞经３００或５００ｍＧｙ５Ｒ后１２ｈ，两种酶活性都明显增高；大鼠全身１５０～５００ｍＧｙ照后２４ｈ，脾细胞ＣｕＺｎ一ＳＯＤ活性也明显增高。上述结果提示，低剂量照射后脾细胞抗氧化酶活性增高可能是一种抗辐射损伤的保护性反应。     

RADIATION HORMESIS A NEW CONCEPT IN RADIOLOGICAL SCIENCE

Low-dose ionizing radiation caused definite stimulation of immune reactions both in humans and mice. The PFC reaction in response to SRBC immunization and the NK activity of the splenocytes were significantly enhanced after low-dose whole body irradiation. Activation of the T lymphocytes, especially the TH, with increased production of IL-2, might be a critical step in the whole process of immunoenhancement. A single dose of 75 mGy X-rays caused significant lowering of hypothalamic M-Enk content as well as serum corticosterone level. The increased serum testosterone level would exert an inhibitory influence on the CRF-ACTH-CS system to keep the blood corticosterone at a lower than normal level which might facilitate the immune reactions in the SRBC-immunized animals. The increased catecholamines in the spleen would probably reinforce this effect resulting in immunoenhancement. Low-dose ionizing radiation caused increased repair of the genetic material at both the molecular and subcellular levels. The UDS of human and murine lymphocytes was augmented by single or continuous low-dose irradiation. The stimulation of DNA polymerase activity might be responsible for such effects. Exposure to very small doses of low LET radiation could induce in different tissues an adaptive response which alleviated chromosome damage caused by subsequent larger dose radiation. Such an adaptive response could be induced both in vivo and in vitro in different animal species. The induced adaptive response faded away after 3 cell cycles could be re-induced by a second exposure to low-dose radiation. The mechanism of the inductive process needs further study.(ABSTRACT TRUNCATED AT 250 WORDS)     

低剂量辐射诱导小鼠睾丸细胞中IRE1α和XBP1 mRNA及其蛋白的表达

目的：检测小鼠睾丸细胞中肌醇需求酶1α（IRE1α）和X盒结合蛋白1（XBP1）mRNA和蛋白的表达,探讨IRE1-XBP1通路激活在低剂量辐射（LDR）诱导小鼠睾丸细胞内质网应激中的作用。方法：50只健康雄性ICR小鼠,随机分为10组,经75 mGy X射线全身照射后不同时间（0、3、6、12和24h）及不同剂量（0、50、75、100和200 mGy）X射线照射后12 h处死,分别采用实时定量PCR法和Western blotting法检测小鼠睾丸细胞中IRE1α、Total-XBP1（T-XBP1）和Spliced-XBP1（S-XBP1）mRNA表达水平及蛋白表达强度。结果：75 mGy X射线照射后0~24 h,小鼠睾丸细胞中IRE1α、T-XBP1和S-XBP1 mRNA（除了3 h时T-XBP1和S-XBP1 mRNA）表达水平均随时间延长而升高,并在6 h时达到峰值,而后逐渐降低;与0 h组比较,6、12和24 h组IRE1α mRNA、6和12 h组T-XBP1 mRNA及S-XBP1 mRNA表达水平均明显升高（P<0.05或P<0.01）。与0 h组比较,不同时间组IRE1α和S-XBP1蛋白表达强度升高,6和12 h组IRE1α蛋白表达强度升高最明显,24 h组S-XBP1蛋白表达强度升高最明显,而T-XBP1蛋白表达强度稍有降低。0~200 mGy照射后12 h,小鼠睾丸细胞中IRE1α、T-XBP1和S-XBP1 mRNA表达水平升高,75 mGyX射线照射后升高达峰值后逐渐降低,甚至降至0 mGy以下;与0 mGy组比较,75和200 mGy组小鼠睾丸细胞中IRE1α、75 mGy组小鼠睾丸细胞中T-XBP1和S-XBP1mRNA表达水平明显升高（P<0.05或P<0.01）。与0 mGy组比较,75 mGy组IRE1α和S-XBP1蛋白表达强度升高,75和200 mGy组小鼠睾丸细胞中S-XBP1蛋白表达强度升高最明显,而T-XBP1蛋白表达强度无明显变化。结论：LDR可诱导小鼠睾丸细胞中IRE1α和S-XBP1 mRNA表达水平和蛋白表达强度增加,从而激活内质网应激中的IRE1-XBP1信号通路。     

131I近距离放射对C6胶质瘤细胞杀伤的实验研究

目的 探讨131I近距离放射杀伤培养C6胶质瘤细胞的有效剂量率及有效剂量,指导治疗计划.方法 将负载活度60mCi 131I的放疗囊置于距离培养的C6胶质瘤细胞5mm、30mm处照射,持续72h/次,每隔4d用Annexin V-FITC/PI双染、流式细胞术以及克隆形成率法检测照射后C6胶质瘤细胞的凋亡率和细胞存活分数.结果 照射72h后能诱导部分瘤细胞凋亡,凋亡率可达16.42％±1.66％;瘤细胞存在增殖性死亡现象;瘤细胞存活分数在72h照射后下降,最低为59.0％±2.39％;在131I近距离放射时,较低剂量率(＜400mGy/h)情况下,也可诱发C6胶质瘤细胞凋亡.在剂量率186.6-677.8mGy/h区间,随剂量率加大凋亡率反而减小.诱导瘤细胞凋亡的有效吸收剂量率应≥47.64-61.65mGy/h,72h累计吸收剂量≥3.9Gy.结论 放疗囊负载131I近距离照射72h后可诱发C6胶质瘤细胞部分凋亡,瘤细胞存活分数下降.诱导C6胶质瘤细胞凋亡的有效剂量率应≥47.64-61.65mGy/h,72h有效累计吸收剂量≥3.9Gy.