-
在大规模核与辐射应急事故发生的早期,对大量疑似受照人群进行快速准确的分类诊断和剂量估算是事故救援的关键所在。染色体畸变分析和微核分析等细胞遗传学方法是目前最常用的估算受照者生物剂量的生物剂量计,这些方法稳定性好、灵敏度高,但耗时过长,不能满足大规模辐射事故分类诊断和剂量估算的需求,快速、高通量的生物剂量学指标引起了广泛关注。近年来,随着分子生物学技术与理论的飞速发展、有关生物大分子的生物剂量计研究亦不断深入。分子生物学水平的生物剂量学指标的研究主要围绕电离辐射所致的DNA损伤、基因表达水平和蛋白质水平的改变展开。本文就近年来分子生物学水平的生物剂量学指标的研究进展进行概述。
分子生物学水平的生物剂量学指标研究现状
Research status of biological dosimetry index of molecular biological level
-
摘要: 生物剂量学指标在核事故受照人员剂量估算及辐射生物效应研究中具有重要作用,而现有的染色体畸变分析不能满足大量快速检测的需求。因此,寻找快速、简便、高通量的生物剂量学指标成为放射生物学研究的热点。随着分子生物学技术与理论的飞速发展,有关生物大分子的辐射效应研究亦不断深入,分子生物学水平的生物剂量学指标的研究主要围绕电离辐射所致的DNA损伤、基因表达水平和蛋白质水平改变展开。笔者就近年来分子生物学水平的生物剂量学指标的研究进行综述。Abstract: Biological dosimetry indicators play important roles in the dose estimation of irradiated personnel in nuclear accident and in the study of radiation biological effects. However, chromosome aberration analysis cannot satisfy the requirements of mass rapid detection. Therefore, determining fast, simple, and high-throughput biodosimetry indicators has become a hot spot in radiobiology. With the rapid development in molecular biology technology and theory, the radiation effects of biological macromolecules have been studied extensively. The biological dosimetry of molecular biological level is mainly focused on the DNA damage induced by ionizing radiation, that is, the changes in gene expression and protein levels. This paper reviews the recent advances in biodosimetry at molecular biological level.
-
Key words:
- Radiation, ionizing /
- Genes /
- DNA damage /
- Biodosimeter
-
[1] Riches LC, Lynch AM, Gooderham NJ. Early events in the mammalian response to DNA double-strand breaks[J]. Mutagenesis, 2008, 23(5):331-339. doi: 10.1093/mutage/gen039 [2] 田梅, 潘艳, 刘建香, 等. γ射线诱导人淋巴细胞损伤及磷酸化组蛋白H2AX和ATM表达[J].中华放射医学与防护杂志, 2011, 31(2):126-129.
Tian M, Pan Y, Liu JX, et al. Human lymphocyte damage and phosphorylation of H2AX and ATM induced by γ-rays[J]. Chin J Radiol Med Prot, 2011, 31(2):126-129.[3] Horn S, Barnard S, Rothkamm K. Gamma-H2AX-based dose estimation for whole and partial body radiation exposure[J/OL]. PLoS One, 2011, 6(9): 1-8[2017-12-19]. http://www.plosone.org. DOI: 10.1371/journal.pone.0025113. [4] Roch-Lefevre S, Mandina T, Voisin P, et al. Quantification of gamma-H2AX foci in human lymphocytes:a method for biological dosimetry after ionizing radiation exposure[J]. Radiat Res, 2010, 174(2):185-194. DOI:10.1667/RR1775.1. [5] 潘艳, 高刚, 刘澜涛, 等.钴-60伽玛射线诱导淋巴细胞γ H2AX表达的研究[J].辐射研究与辐射工艺学报杂志, 2014, 32(2):9-12.
Pan Y, Gao G, Liu LT, Study on γH2AX expression of human lymphocytes induced by 60Co gamma-rays[J]. J Radiat Res Radiat Process, 2014, 32(2):9-12.[6] Wang J, He L, Fan D, et al. Establishment of a γ-H2AX foci-based assay to determine biological dose of radon to red bone marrow in rats[J/OL]. Sci Rep, 6: 30018[2017-12-19]. http://www.nature.com/articles/srep30018. DOI: 10.1038/srep30018. [7] Zhang J, He Y, Shen X, et al. γ-H2AX responds to DNA damage induced by long-term exposure to combined low-dose-rate neutron and γ-ray radiation[J]. Mutat Res, 2016, 795(1):36-40. DOI:10.1016/j.mrgentox.2015.11.004. [8] Vandersickel V, Beukes P, Van Bockstaele B, et al. Induction and disappearance of γH2AX foci and formation of micronuclei after exposure of human lymphocytes to 60Co γ-rays and p(66)+ Be(40) neutrons[J]. Int J Radiat Biol, 2014, 90(2):159-68. DOI:10.3109/09553002.2014.860252. [9] Solovjeva L, Firsanov D, Pleskach N, et al. Immunofluorescence analysis of γ-H2AX foci in mammalian fibroblasts at different phases of the cell cycle[J]. Methods Mol Biol, 2017, 1644:187-194. DOI:10.1007/978-1-4939-7187-9_17. [10] Hopp N, Hagen J, Aggeler B, et al. Express γ-H2AX immunocyto chemical detection of DNA damage[J]. Methods Mol Biol, 2017, 1644:123-128. DOI:10.1007/978-1-4939-7187-9_10. [11] Firsanov D, Solovjeva L, Lublinskaya O, et al. Rapid detection of γ-H2AX by flow cytometry in cultured mammalian cells[J]. Methods Mol Biol, 2017, 1644:129-138. DOI:10.1007/978-1-4939-7187-9-11. [12] 李明娟, 王维维, 陈士伟, 等.辐射小鼠血细胞ATM、CDKN1A、DDB2和GADD45A基因表达分析[J].辐射研究与辐射工艺学报, 2011, 29(2):93-98.
Li MJ, Wang WW, Chen SW, et al. Analysis of the expression of ATM、CDKNIA、DDB2 and GADD45A genes in irradiated mouse blood cells[J]. J Radiat Res Radiat Process, 2011, 29(2):93-98.[13] Ostling O, Johanson KJ. Microelectrophoretic study of radiation-induced DNA damages in individual mammalian cells[J]. Biochem Biophys Res Commun, 1984, 123(1):291-298. DOI:10.1016/0006-291X(84)90411-X. [14] Singh N, Mccoy M, Tice R, et al. A simple technique for quantitation of low level of DNA damage in individual cells[J]. 1988, 175(1): 184-191. DOI: 10.1016/0014-4827(88)90265-0. [15] Zheng W, He JL, Jin LF, et al.Assessment of human DNA repair(NER) capacity with DNA repair rate(DDR) by comet assay[J].Biomed Environ Sci, 2005, 18(2):117-123. [16] 段志凯, 时爱丽, 刘建功, 等, 单细胞凝胶电泳技术用于估算大剂量电离辐射的初步探索[J].癌变·畸变·突变, 2011, 23(6):442-445. DOI:10.3969/j.issn.1004-616x.2011.06.009.
Duan ZK, Shi AL, Liu JG, et al. High dose radiation-induced DNA damage using single cell gel electrophoresis[J]. Carcinog Teratog Mutag, 2011, 23(6):442-445. doi: 10.3969/j.issn.1004-616x.2011.06.009[17] Sowmithra K, Shetty NJ, Jha SK, et al. Evaluation of genotoxicity of the acute gamma radiation on earthworm Eisenia fetida using single cell gel electrophoresis technique (Comet assay)[J]. Mut Res, 2015, 794:52-56. DOI:10.1016/j.mrgentox.2015.10.001. [18] Sugihara T, Magae J, Wadhwa R, et al. Dose and dose-rate effects of low-dose ionizing radiation on activation of Trp53 in immortalized murine cells[J]. Radiat Res, 2004162(3):296-307. [19] Manning G, Kabacik S, Finnon P, et al. High and low dose responses of transcriptional biomarkers in ex vivo X-irradiated human blood[J]. Int J Radiat Biol, 2013, 89(7):512-522. DOI:10.3109/09553002. 2013.769694. [20] 何颖, 沈先荣, 钱甜甜, 等.低剂量γ射线对人淋巴母细胞CCNG1基因表达的影响[J].解放军医学杂志, 2015, 40(6):498-501. DOI:10.11855/j.issn.0577-7402.2015.06.16.
He Y, Shen XR, Qian TT. Effects of low-dose γ-ray on the expression of CCNG1 gene in human lymphoblasts[J]. Med J Chin PLA, 2015, 40(6):498-501. doi: 10.11855/j.issn.0577-7402.2015.06.16[21] Turtoi A, Brown I, Oskamp D, et al. Early gene expression in human lymphocytes after gamma-irradiation-a genetic pattern with potential for biodosimetry[J]. Int J Radiat Biol, 2008, 84(5):375-387. DOI:10.1080/09553000802029886. [22] 金顺子, 武宁, 刘丽波, 等.辐射诱导细胞周期调控和DNA损伤反应相关基因表达变化的实验研究[J].辐射防护, 2010, 30(2):70-79.
Jin SZ, Wu N, Liu LB, et al. Experimental study on changes of gene expression related to radiation-induced cell cycle regulation and DNA damage response[J]. Radiat Prot, 2010, 30(2):70-79.[23] 李洁清, 李坤, 封丽, 等. X射线照射AHH-1细胞基因表达转录谱变化研究[J].中国职业医学, 2013, 40(5):420-426.
Li JQ, Li K, Feng L, et al. Study on alterations of gene transcriptional profiles in AHH-1 cells by X-ray exposure[J]. China Occupat Med, 2013, 40(5):420-426.[24] 刘建功, 党旭红, 张忠新, 等. 60Co γ射线对人离体外周血CDKN1A基因表达水平的影响[J].辐射防护通讯, 2015, 35(2):13-15.
Liu JG, Dang XH, Zhang ZX, et al. A study on gene expression of CDKN1A from human peripheral blood induced by 60Co γ-rays[J]. Radiat Prot Bulletin, 2015, 35(2):13-15.[25] Yu M. Somatic mitochondrial DNA mutations in human cancers[J]. Adv Clin Chem, 2012, 57:99-138. DOI:10.1016/B978-0-12-394384-2.00004-8. [26] Rahmani B, Azimi C, Omranipour R, et al. Mutation screening in the mitochondrial D-loop region of tumoral and non-tumoral breast cancer in iranian patients[J]. Acta Med Iran, 2012, 50(7):447-453. [27] Yoshida T, Goto S, Kawakatsu M, et al. Mitochondrial dysfunction, a probable cause of persistent oxidative stress after exposure to ionizing radiation[J]. Free Radic Res, 2012, 46(2):147-153. DOI:10.3109/10715762.2011.645207. [28] Wen Q, Hu Y, Ji F, et al. Mitochondrial, DNA alterations of peripheral lymphocytes in acute lymphoblastic leukemia patients undergoing total body irradiation therapy[J]. Radiat Oncol, 2011, 6:133. DOI:10.1186/1748-717X-6-133. [29] 张忠新, 刘建功, 张淑贤, 等.电离辐射对人外周血线粒体编码基因mRNA表达的影响[J].癌变·畸变·突变, 2013, 25(1):22-25, 30.
Zhang ZX, Liu JG, Zhang SX, et al. Effects of radiation on mitochondrial gene expression in human peripheral blood cells[J]. Carcinog Teratog Mutag, 2013, 25(1):22-25, 30.[30] Girardi C, Pitta CD, Casara S, et al. Analysis of miRNA and mRNA expression profiles highlights alterations in ionizing radiation response of human lymphocytes under modeled microgravity[J/OL]. PLoS One, 2012, 7(2): e31293[2017-12-19]. www.plosone.org. DOI: 10.1371/journal.pone.0031293. [31] Beer L, Seemann R, Ristl R, et al. High dose ionizing radiation regulates micro RNA and gene expression changes in human peripheral blood mononuclear cells[J]. BMC Genomics, 2014, 15:814. DOI:10.1186/1471-2164-15-814. [32] 李刚强, 朱瑞, 周海亚, 等. 60Co γ亚致死量辐射致小鼠外周血中microRNA表达改变的研究[J].中华灾害救援医学, 2015, 3(11):615-618.
Li GQ, Zhu R, Zhou HY, et al. Study on microRNA changes induced by sublethal dose of 60Co γ ray on mouse[J]. Chin J Dis Med, 2015, 3(11):615-618.[33] 李刚强, 朱瑞, 周海亚, 等. 60Co γ辐射致小鼠血液中microRNA表达改变及意义[J].河南预防医学杂志, 2016, 27(6):401-405.
Li GQ, Zhu R, Zhou HY. MicroRNA changes induced by radiation in mouse[J]. Henan J Prev Med, 2016, 27(6):401-405.[34] Sharma M, Moulder JE. The urine proteome as a radiation biodosimeter[J]. Adv Exp Med Biol, 2013, 990:87-100. DOI:10.1007/978-94-007-5896-4_5. [35] Partridge MA, Chai Y, Zhou H. High-throughput antibody-based assays to identify and quantify radiation-responsive protein biomarkers[J]. Int J Radiat Biol, 2010, 86(4):321-328. DOI:10.3109/09553000903564034. [36] Deperas-Kaminska M, Bajinskis A, Marczyk M, et al. Radiation-induced changes in levels of selected proteins in peripheral blood serum of breast cancer patients as a potential triage biodosimeter for large-scale radiological emergencies[J]. Health Physics, 2014, 107(6):555-563. DOI:10.1097/HP.0000000000000158.
计量
- 文章访问数: 3792
- HTML全文浏览量: 2697
- PDF下载量: 2