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。     

Effect of Cycloheximide on the Adaptive Response Induced by Low Dose Radiation

Human lymphocytes pre-exposed to 10 mGy or 50mGy of X-rays become less sensitive to subsequent large dose irradiation,exhibited lower rate of chromosome aberration than expected.This adaptive response could be inhibited by cycloheximide,a protein synthesis inhibitor for successive 2h period ranging from 0.5h before to 4h after the low dose exposure,indicating that the adaptive response was directly related with the protein synthesis.     

“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。     

Study on the mechanism of cytogenetic adaptive response induced by low dose radiation.

Pre-exposure of human lymphocytes to low dose radiation (D1) could induce a cytogenetic adaptive response expressed as a decrease of chromatid aberrations caused by subsequent large dose radiation (D2). There are two possible explanations for its mechanism, i.e., activation of enzymatic processes by D1 facilitating repair of chromosomal damage and induction of protective proteins by D1 reducing the number of chromosomal aberrations. The results here showed: (1) the cytogenetic adaptive response could be enhanced by hyperthermia (41 degrees C and 43 degrees C) and suppressed by hypothermia (4 degrees C); (2) hyperthermia (41 degrees C) alone could also induce the cytogenetic adaptive response; (3) the cytogenetic adaptive response could be inhibited by cycloheximide--an inhibitor of protein synthesis; (4) supernatant from cultured lymphocytes treated with D1 failed to show the protective effect. The results imply that the cytogenetic adaptive response is not only related to the activation of repair enzymes, but also to the induction of protective proteins.

     

CROSS-RESISTANCE INDUCED BY LOW DOSEX-RAYS OR LOW CONCENTRATION OF MMCIN SOMATIC AND GERM CELLS

<正> It was reported that low concentration of MMC as Dl could induce an adaptive response in human lymphocytes in vitro. When mice were exposed to 10 or 50 mGy X-rays , the bone marrow or germ cells exhibited less frequencies of chromatid aberration induced by 0. 5,2. 5 or 5. 0 mg/kg of MMC as D2 in vivo condition. The present study was for the first time to examine the cross-resistance between the radiation and chemical mutagens in vivo condition in both somatc and germ cells.     

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。     

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)     

低水平~(60)Co-γ射线全身照射诱导家兔外周血淋巴细胞的遗传学适应性反应研究

用~(60)Co-γ射线对家兔进行慢性全身均匀照射,当累积剂量分别达到0.3、0.75、0.9、1.2、1.5、1.8Gy时,取外周血G_o期和G_2期淋巴细胞,再均以1.5Gy X射线照射。制备染色体标木观察有无适应性反应及其剂量范围。结果证明D_1+D_2(G_o期)组,D_1在0.3～1.5Gy之间;D_1+D_2(G_2期)组D_1在0.3～1.2Gy剂量范围内均可诱导出明显地适应性反应。     

肿瘤接种前,后低电离辐射对肿瘤转移的影响

Ｃ５７ＢＬ小鼠接受２５、５０、７５、１００ｍＧｙＸ线单次全身照射后，小鼠肺转移疆节数明显低于对照组，其中以７５ｍＧｙ组最低，再将荷瘤小鼠进行７５ｍＧｙＸ线照射，受照组肺转移结节数仍低于对照组。与此同时发现，７５ｍＧｙ照射的小鼠免疫功能明显增强。上述结果提示：小剂量电离辐射对肿瘤转移有抑制作用，其可能机制是其免疫刺激效应。     

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。     

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。     

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。     

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。     

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     

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。     

Immunoenhancement in tumor-bearing mice induced by whole body X-irradiation with 75 mGy

目的 :本研究观察低剂量全身照射对荷瘤小鼠免疫功能的影响。方法 :C57BL/6J小鼠右后肢肌肉内接种 Lewis肺癌细胞 ,1 0 d后给予 75m Gy X射线全身照射 ,在照射后 1 8h处死小鼠并采用3 H- Td R掺入法或释放法测定荷瘤小鼠的胸腺细胞自发增殖力、脾细胞对 Con A和 LPS的反应性、脾脏内特异性细胞毒性淋巴细胞 ( CTL )和自然杀伤细胞 ( NK)以及淋巴因子激活的杀伤细胞 ( LAK)的细胞毒效应。结果 :75m Gy X射线全身照射后荷瘤小鼠的上述免疫学参数明显高于假照射荷瘤小鼠 ( P<0 .0 1 )。结论 :低剂量辐射可显著提高荷瘤小鼠的免疫功能 ,可能在癌症防治中具有实际应用意义     

低剂量辐射离体照射诱导脾细胞免疫适应性反应的研究

目的：观察低剂量辐射离体照射能否诱导小鼠脾细胞的免疫适应性反应。方法：采用3H-TdR掺入法。结果：未发现0．025～0．075Gy低剂量辐射明显降低6h后0．75Gy或1．0Gy攻击剂量所致脾细胞丝裂原反应（ConA或LPS）的损伤作用，而整体实验中上述照射条件则能诱导免疫适应性反应。结论：说明整体调节在诱导小鼠脾细胞丝裂原反应的适应性中可能起重要作用。