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自1895年德国科学家伦琴发现X射线以来,辐射技术在人类生活中得到了广泛的应用,放疗已成为临床肿瘤治疗中的重要手段。近20年来,研究者的研究结果发现,电离辐射除了可通过与细胞直接作用引起DNA损伤等效应之外,还可引起基因组的不稳定性、远位效应和旁效应等非靶效应[1],这些非靶效应同样影响辐射的进程与结果,最终对机体产生重要影响。科学家对中国仓鼠卵巢细胞(CHO)的研究结果发现,尽管只有0.1%~1%的细胞受到α粒子的照射,但是在其他未受照射的30%~50%的细胞中也可产生姐妹染色单体交换这种DNA损伤,这一发现揭开了辐射旁效应(radiation-induced bystander effects,RIBE)研究的序幕,引起了研究者的研究兴趣,其发生的途径和机制也得到了深入地研究和阐释[2]。免疫系统作为生物体重要的免疫监视与防御系统,也参与到了RIBE的发展过程之中。明确免疫系统在RIBE中的作用及其机制,对完善放射生物学的理论体系具有重要的科学意义。
免疫系统在辐射旁效应中的作用研究进展
Research progress on the role of immune system in radiation-induced bystander effect
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摘要: 辐射旁效应(RIBE)自被发现以来,一直是辐射生物学领域的研究热点。目前已得到证实,RIBE可通过细胞间缝隙连接通讯和可溶性细胞分泌物等途径传递。近年来的研究结果发现,免疫系统在RIBE中扮演着重要角色,深刻影响着辐射生物学效应的进程与结果。笔者就免疫系统在RIBE中的作用进行综述,以期为RIBE的相关研究提供一定的理论基础。Abstract: Radiation-induced bystander effect (RIBE) has been a research hotspot in the field of radiation biology since it was discovered. It has been demonstrated that RIBE can be mediated by gap junctional communication and soluble cell secretions. Recent studies show that the immune system plays an important role in the progress of RIBE, profoundly affecting the progress and results of biological effect of radiation. In this paper, the role of the immune system in the RIBE is briefly reviewed, with a view to providing a theoretical basis for the study of RIBE.
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Key words:
- Radiation /
- Bystander effect /
- Immune system
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[1] Nalewajska M, Marchelek-Myśliwiec M, Opara-Bajerowicz M, et al. Connexins-therapeutic targets in cancers[J/OL]. Int J Mol Sci. 2020, 21(23): 9119[2019-11-04]. https://www.mdpi.com/1422-0067/21/23/9119. DOI: 10.3390/ijms21239119. [2] Sprung CN, Ivashkevich A, Forrester HB, et al. Oxidative DNA damage caused by inflammation may link to stress-induced non-targeted effects[J]. Cancer Lett, 2015, 356(1): 72−81. DOI: 10.1016/j.canlet.2013.09.008. [3] Peng Y, Zhang M, Zheng L, et al. Cysteine protease cathepsin B mediates radiation-induced bystander effects[J]. Nature, 2017, 547(7664): 458−462. DOI: 10.1038/nature23284. [4] Prise KM, O'Sullivan JM. Radiation-induced bystander signalling in cancer therapy[J]. Nat Rev Cancer, 2009, 9(5): 351−360. DOI: 10.1038/nrc2603. [5] Mladenov E, Li F, Zhang L, et al. Intercellular communication of DNA damage and oxidative status underpin bystander effects[J]. Int J Radiat Biol, 2018, 94(8): 719−726. DOI: 10.1080/09553002.2018.1434323. [6] Yang SN, Xu J, Shao WX, et al. Radiation-induced bystander effects in A549 cells exposed to 6 MV X-rays[J]. Cell Biochem Biophys, 2015, 72(3): 877−882. DOI: 10.1007/s12013-015-0555-2. [7] 杨雪娇, 施文玉, 马佳艳, 等. 受照脑胶质瘤细胞诱导神经干细胞旁效应[J]. 中华放射医学与防护杂志, 2020, 40(9): 659−665. DOI: 10.3760/cma.j.issn.0254-5098.2020.09.002.
Yang XJ, Shi WY, Ma JY, et al. Irradiated glioma cells induce bystander effects in neural stem cells[J]. Chin J Radiol Med Prot, 2020, 40(9): 659−665. DOI: 10.3760/cma.j.issn.0254-5098.2020.09.002.[8] Fardid R, Najafi M, Salajegheh A, et al. Radiation-induced non-targeted effect in vivo: evaluation of cyclooygenase-2 and endothelin-1 gene expression in rat heart tissues[J]. J Cancer Res Ther, 2017, 13(1): 51−55. DOI: 10.4103/0973-1482.203601. [9] Koturbash I, Rugo RE, Hendricks CA, et al. Irradiation induces DNA damage and modulates epigenetic effectors in distant bystander tissue in vivo[J]. Oncogene, 2006, 25(31): 4267−4275. DOI: 10.1038/sj.onc.1209467. [10] Dong C, He MY, Tu WZ, et al. The differential role of human macrophage in triggering secondary bystander effects after either gamma-ray or carbon beam irradiation[J]. Cancer Lett, 2015, 363(1): 92−100. DOI: 10.1016/j.canlet.2015.04.013. [11] Ji KH, Wang Y, Du LQ, et al. Research progress on the biological effects of low-dose radiation in china[J]. Dose Response, 2019, 17(1): 1−16. DOI: 10.1177/1559325819833488. [12] Verma N, Tiku AB. Significance and nature of bystander responses induced by various agents[J]. Mutat Res, 2017, 773: 104−121. DOI: 10.1016/j.mrrev.2017.05.003. [13] Ariyoshi K, Miura T, Kasai K, et al. Radiation-induced bystander effect is mediated by mitochondrial DNA in exosome-like vesicles[J/OL]. Sci Rep, 2019, 9(1): 9103[2019-11-04]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591216. DOI: 10.1038/s41598-019-45669-z. [14] Jacob A, Shah KG, Wu RQ, et al. Ghrelin as a novel therapy for radiation combined injury[J]. Mol Med, 2010, 16(3/4): 137−143. DOI: 10.2119/molmed.2009.00154. [15] 李德冠, 唐卫生, 牟感恩, 等. 5-甲氧基色胺-α-硫辛酸盐对6.0 Gy受照小鼠造血系统的辐射防护作用[J]. 国际放射医学核医学杂志, 2017, 41(1): 19−22, 32. DOI: 10.3760/cma.j.issn.1673-4114.2017.01.004.
Li DG, Tang WS, Mu GE, et al. Protective effects of 5-methoxytryptamine-α-lipoic acid salt on mice exposed to 6.0 Gy total body irradiation[J]. Int J Radiat Med Nucl Med, 2017, 41(1): 19−22, 32. DOI: 10.3760/cma.j.issn.1673-4114.2017.01.004.[16] Parkin J, Cohen B. An overview of the immune system[J]. Lancet, 2001, 357(9270): 1777−1789. DOI: 10.1016/S0140-6736(00)04904-7. [17] Diegeler S, Hellweg CE. Intercellular communication of tumor cells and immune cells after exposure to different ionizing radiation qualities[J/OL]. Front Immunol, 2017, 8: 664[2019-11-04]. https://www.frontiersin.org/articles/10.3389/fimmu.2017.00664/full. DOI: 10.3389/fimmu.2017.00664. [18] Stoecklein VM, Osuka A, Ishikawa S, et al. Radiation exposure induces inflammasome pathway activation in immune cells[J]. J Immunol, 2015, 194(3): 1178−1189. DOI: 10.4049/jimmunol.1303051. [19] McBride WH, Schaue D. Radiation-induced tissue damage and response[J]. J Pathol, 2020, 250(5): 647−655. DOI: 10.1002/path.5389. [20] El-Din MAA, Abdelrazzak AB, Ahmed MT, et al. Radiation induced bystander effects in the spleen of cranially-irradiated rats[J]. Br J Radiol, 2017, 90(1080): 20170278. DOI: 10.1259/bjr.20170278. [21] Laskin DL, Malaviya R, Laskin JD. Role of macrophages in acute lung injury and chronic fibrosis induced by pulmonary toxicants[J]. Toxicol Sci, 2019, 168(2): 287−301. DOI: 10.1093/toxsci/kfy309. [22] Fu JM, Wang J, Wang XD, et al. Signaling factors and pathways of α-particle irradiation induced bilateral bystander responses between Beas-2B and U937 cells[J]. Mutat Res, 2016, 789: 1−8. DOI: 10.1016/j.mrfmmm.2016.04.004. [23] Calveley VL, Khan MA, Yeung IWT, et al. Partial volume rat lung irradiation: temporal fluctuations of in-field and out-of-field DNA damage and inflammatory cytokines following irradiation[J]. Int J Radiat Biol, 2005, 81(12): 887−899. DOI: 10.1080/09553000600568002. [24] Christersdottir T, Pirault J, Gisterå A, et al. Prevention of radiotherapy-induced arterial inflammation by interleukin-1 blockade[J]. Eur Heart J, 2019, 40(30): 2495−2503. DOI: 10.1093/eurheartj/ehz206. [25] Liu YC, Zou XB, Chai YF, et al. Macrophage polarization in inflammatory diseases[J/OL]. Int J Biol Sci, 2014, 10(5): 520−429[2019-11-04]. https://www.ijbs.com/v10p0520.htm. DOI: 10.7150/ijbs.8879. [26] Wu X, Ji HY, Wang YL, et al. Melatonin alleviates radiation-induced lung injury via regulation of miR-30e/NLRP3 axis[J/OL]. Oxid Med Cell Longev, 2019, 2019: article ID 4087298, 14 pages[2019-11-04]. https://www.hindawi.com/journals/omcl/2019/4087298. DOI: 10.1155/2019/4087298. [27] Lei RH, Zhao T, Li Q, et al. Carbon ion irradiated neural injury induced the peripheral immune effects in vitro or in vivo[J/OL]. Int J Mol Sci, 2015, 16(12): 28334−28346[2019-11-04]. https://www.mdpi.com/1422-0067/16/12/26109. DOI: 10.3390/ijms161226109. [28] Demaria S, Ng B, Devitt ML, et al. Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated[J]. Int J Radiat Oncol Biol Phys, 2004, 58(3): 862−870. DOI: 10.1016/j.ijrobp.2003.09.012. [29] 朱志超, 白煜, 卢绪章, 等. Olaparib对HL-60细胞NKG2D配体表达的调节作用及相关机制研究[J]. 中国实验血液学杂志, 2020, 28(6): 1826−1830. DOI: 10.19746/j.cnki.issn1009-2137.2020.06.006.
Zhu ZC, Bai Y, Lu XZ, et al. Effects and mechanism of PARP inhibitor olaparib on the expression of NKG2D ligands in HL-60 cells[J]. J Exp Hematol, 2020, 28(6): 1826−1830. DOI: 10.19746/j.cnki.issn1009-2137.2020.06.006.[30] Herrera FG, Bourhis J, Coukos G. Radiotherapy combination opportunities leveraging immunity for the next oncology practice[J]. CA Cancer J Clin, 2017, 67(1): 65−85. DOI: 10.3322/caac.21358. [31] Lierova A, Jelicova M, Nemcova M, et al. Cytokines and radiation-induced pulmonary injuries[J]. J Radiat Res, 2018, 59(6): 709−753. DOI: 10.1093/jrr/rry067. [32] Hu HH, Chen DQ, Wang YN, et al. New insights into TGF-β/Smad signaling in tissue fibrosis[J]. Chem Biol Interact, 2018, 292: 76−83. DOI: 10.1016/j.cbi.2018.07.008. [33] Shao C, Folkard M, Prise KM. Role of TGF-β1 and nitric oxide in the bystander response of irradiated glioma cells[J]. Oncogene, 2008, 27(4): 434−440. DOI: 10.1038/sj.onc.1210653. [34] Luo J, Hu SN, Wei TT, et al. TGF-beta 1 levels are associated with lymphocyte percentages in patients with lung cancer treated with radiation therapy[J/OL]. Onco Targets Ther, 2018, 11: 8349−8355[2019-11-04]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267770. DOI: 10.2147/OTT.S175956. [35] Hei TK, Zhou HN, Chai YF, et al. Radiation induced non-targeted response: mechanism and potential clinical implications[J]. Curr Mol Pharmacol, 2011, 4(2): 96−105. DOI: 10.2174/1874467211104020096. [36] Pine SR, Mechanic LE, Enewold L, et al. Differential serum cytokine levels and risk of lung cancer between african and european americans[J]. Cancer Epidemiol Biomarkers Prev, 2016, 25(3): 488−497. DOI: 10.1158/1055-9965.EPI-15-0378. [37] Lepleux C, Marie-Brasset A, Temelie M, et al. Bystander effectors of chondrosarcoma cells irradiated at different LET impair proliferation of chondrocytes[J]. J Cell Commun Signal, 2019, 13(3): 343−356. DOI: 10.1007/s12079-019-00515-9. [38] Shiraishi K, Ishiwata Y, Nakagawa K, et al. Enhancement of antitumor radiation efficacy and consistent induction of the abscopal effect in mice by ECI301, an active variant of macrophage inflammatory protein-1α[J]. Clin Cancer Res, 2008, 14(4): 1159−1166. DOI: 10.1158/1078-0432.CCR-07-4485. [39] Johnston CJ, Williams JP, Okunieff P, et al. Radiation-induced pulmonary fibrosis: examination of chemokine and chemokine receptor families[J]. Radiat Res, 2002, 157(3): 256−265. DOI: 10.1667/0033-7587(2002)157[0256:ripfeo]2.0.co;2. [40] Schaue D, Kachikwu EL, McBride WH. Cytokines in radiobiological responses: a review[J]. Radiat Res, 2012, 178(6): 505−523. DOI: 10.1667/RR3031.1. [41] Hei TK, Zhou HN, Ivanov VN, et al. Mechanism of radiation-induced bystander effects: a unifying model[J]. J Pharm Pharmacol, 2008, 60(8): 943−950. DOI: 10.1211/jpp.60.8.0001. [42] Breen WG, Leventakos K, Dong H, et al. Radiation and immunotherapy: emerging mechanisms of synergy[J]. J Thorac Dis, 2020, 12(11): 7011−7023. DOI: 10.21037/jtd-2019-cptn-07. [43] Reits EA, Hodge JW, Herberts CA, et al. Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy[J]. J Exp Med, 2006, 203(5): 1259−1271. DOI: 10.1084/jem.20052494.
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