性别和年龄对60Co γ射线照射离体人外周血辐射敏感基因mRNA表达的影响

doi:10.3969/j.issn.1004-616x.2019.06.001

癌变·畸变·突变 ›› 2019, Vol. 31 ›› Issue (6): 421-427.doi: 10.3969/j.issn.1004-616x.2019.06.001

• 论著 • 下一篇

性别和年龄对⁶⁰Co γ射线照射离体人外周血辐射敏感基因mRNA表达的影响

李爽, 陆雪, 封江彬, 田梅, 蔡恬静, 刘青杰

中国疾病预防控制中心辐射防护与核安全医学所, 辐射防护与核应急中国疾病预防控制中心重点实验室, 北京 100088

收稿日期:2019-07-15 修回日期:2019-11-11 出版日期:2019-11-30 发布日期:2019-12-04
通讯作者: 刘青杰,E-mail:liuqingjie@nirp.chinacdc.cn E-mail:liuqingjie@nirp.chinacdc.cn
作者简介:李爽,E-mail:lishuang@nirp.chinacdc.cn。
基金资助:
国家自然科学基金资助项目（81803162，81573081）

Effects of gender and age on expression of radiation-responsive genes in irradiated human peripheral blood samples

LI Shuang, LU Xue, FENG Jiangbin, TIAN Mei, CAI Tianjing, LIU Qingjie

China CDC Key Laboratory of Radiological Protection and Nuclear Emergency, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing 100088, China

Received:2019-07-15 Revised:2019-11-11 Online:2019-11-30 Published:2019-12-04

摘要/Abstract

摘要： 目的：探讨性别和年龄因素对电离辐射诱导的离体人外周血中辐射敏感基因mRNA表达变化的影响。方法：采集30例健康人离体外周血，以剂量率为1 Gy/min的⁶⁰Co γ射线进行照射，照射剂量分别为0.5、1、2、3、4、6和8 Gy （以0 Gy为阴性对照组），照射后培养12 h，应用实时荧光定量PCR （qPCR）方法检测18个辐射敏感基因的mRNA表达水平变化，分析性别和年龄因素对这些基因mRNA表达水平的影响。结果：与阴性对照组相比，各剂量γ射线照射组人外周血18个辐射敏感基因的mRNA表达水平均明显增加，并且呈剂量-效应关系（R²=0.63~0.97，P < 0.05）。在相同照射剂量，MDM2、XPC、FDXR、DDB2、ASTN2和TNFSF4 mRNA相对表达水平在不同个体之间存在较大的差异。女性外周血中BAX、TNFRSF10B、ASTN2、TNFSF4、POLH和GADD45A mRNA相对表达水平均高于男性，在0.5~8 Gy照射剂量范围内具有统计学差异（P < 0.05或P < 0.01）。MDM2、FDXR、DDB2和RPS27L mRNA表达水平在不同年龄组间（20~29岁、30~39岁、40~49岁和50~60岁）存在差异（P < 0.05或P < 0.01）。结论：离体人外周血中辐射敏感基因mRNA表达水平的变化存在个体间差异，且与受照者性别和年龄相关。

关键词: 电离辐射, 基因表达, 性别, 年龄, 个体间差异

Abstract: OBJECTIVE: To investigate the effects of gender and age on the changes in expression of radiation-responsive genes in irradiated human peripheral blood samples. METHODS: Human peripheral blood samples from 30 adult donors was acutely exposed to ⁶⁰Co γ-rays at doses of 0,0.5,1,2,3,4,6 and 8 Gy with the dose rate of 1 Gy/min. Irradiated peripheral blood samples were subsequently incubated at 37-C for 12 h. The effects of gender and age on changes in radiation-responsive gene expressions were analyzed by quantitative real-time polymerase chain reaction (qPCR). RESULTS: The relative mRNA expression levels of 18 radiation-responsive genes were significantly up-regulated in a dose-dependent manner at 12 h after the irradiation (R²=0.63-0.97,P < 0.05). However,the relative mRNA expression levels of MDM2,XPC,FDXR,DDB2,ASTN2 and TNFSF4 showed approximately fivefold variabilities among different individual samples which were irradiated with the same does. Radiation-induced transcriptional changes of BAX,TNFRSF10B,ASTN2,TNFSF4,POLH and GADD45A in female samples were significantly higher than that in male samples (P < 0.05 or P < 0.01). Expression levels of MDM2,FDXR,DDB2 and RPS27L showed differences between four age groups after exposure to 0.5-8 Gy of γ-rays (P < 0.05 or P < 0.01). CONCLUSION: The changes in expression of radiation-responsive genes in blood samples demonstrate significant inter-individual variations which were mainly related to the gender and age of the individual donors.

Key words: ionizing radiation, gene expression, gender, age, inter-individual variation

中图分类号:

Q691

李爽, 陆雪, 封江彬, 田梅, 蔡恬静, 刘青杰. 性别和年龄对⁶⁰Co γ射线照射离体人外周血辐射敏感基因mRNA表达的影响[J]. 癌变·畸变·突变, 2019, 31(6): 421-427.

LI Shuang, LU Xue, FENG Jiangbin, TIAN Mei, CAI Tianjing, LIU Qingjie. Effects of gender and age on expression of radiation-responsive genes in irradiated human peripheral blood samples[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(6): 421-427.

参考文献

[1] SULLIVAN J M, PRASANNA P G, GRACE M B, et al. Assessment of biodosimetry methods for a mass-casualty radiological incident:medical response and management considerations[J]. Health Phys, 2013, 105(6):540-554.;
[2] CHEN B J, DEOLIVEIRA D, SPASOJEVIC I, et al. Growth hormone mitigates against lethal irradiation and enhances hematologic and immune recovery in mice and nonhuman Primates[J]. PLoS One, 2010, 5(6):e11056. DOI:10.1371/journal.pone.0011056.;
[3] FARESE A M, COHEN M V, KATZ B P, et al. Filgrastim improves survival in lethally irradiated nonhuman Primates[J]. Radiat Res, 2013, 179(1):89-100.;
[4] LACOMBE J, S M, AMUNDSON S A, et al. Candidate gene biodosimetry markers of exposure to external ionizing radiation in human blood:A systematic review[J]. PLoS One, 2018, 13(6):e0198851. DOI:10.1371/journal.pone.0198851.;
[5] SPROULL M, CAMPHAUSEN K. State-of-the-art advances in radiation biodosimetry for mass casualty events involving radiation exposure[J]. Radiat Res, 2016, 186(5):423-435.;
[6] MANNING G, MACAEVA E, MAJEWSKI M, et al. Comparable dose estimates of blinded whole blood samples are obtained independently of culture conditions and analytical approaches. Second RENEB gene expression study[J]. Int J Radiat Biol, 2017, 93(1):87-98.;
[7] LI S, ZHANG Q Z, ZHANG D Q, et al. GDF-15 gene expression alterations in human lymphoblastoid cells and peripheral blood lymphocytes following exposure to ionizing radiation[J]. Mol Med Rep, 2017, 15(6):3599-3606.;
[8] LI S, LU X, FENG J B, et al. Identification and validation of candidate radiation-responsive genes for human biodosimetry[J]. Biomed Environ Sci, 2017, 30(11):834-840.;
[9] LIU Q J, ZHANG D Q, ZHANG Q Z, et al. Dose-effect of ionizing radiation-induced PIG3 gene expression alteration in human lymphoblastoid AHH-1 cells and human peripheral blood lymphocytes[J]. Int J Radiat Biol, 2015, 91(1):71-80.;
[10] BRZóSKA K, KRUSZEWSKI M. Toward the development of transcriptional biodosimetry for the identification of irradiated individuals and assessment of absorbed radiation dose[J]. Radiat Environ Biophys, 2015, 54(3):353-363.;
[11] MACAEVA E, MYSARA M, DE VOS W H, et al. Gene expression-based biodosimetry for radiological incidents:assessment of dose and time after radiation exposure[J]. Int J Radiat Biol, 2019, 95(1):64-75.;
[12] KEAM S P, GULATI T, GAMELL C, et al. Biodosimetric transcriptional and proteomic changes are conserved in irradiated human tissue[J]. Radiat Environ Biophys, 2018, 57(3):241-249.;
[13] BALOG R P, CHANG P, JAVITZ H S, et al. Development of a point-of-care radiation biodosimeter:studies using novel protein biomarker panels in non-human Primates[J]. Int J Radiat Biol, 2018:1-12.;
[14] 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.;
[15] AGBENYEGAH S, ABEND M, ATKINSON M J, et al. Impact of inter-individual variance in the expression of a radiation-responsive gene panel used for triage[J]. Radiat Res, 2018, 190(3):226-235.;
[16] WHITNEY A R, DIEHN M, POPPER S J, et al. Individuality and variation in gene expression patterns in human blood[J]. Proc Natl Acad Sci USA, 2003, 100(4):1896-1901.;
[17] CORREA C R, CHEUNG V G. Genetic variation in radiation-induced expression phenotypes[J]. Am J Hum Genet, 2004, 75(5):885-890.;
[18] BAHREYNI-TOOSSI M T, VOSOUGHI H, AZIMIAN H, et al. In vivo exposure effects of ^99mTc-methoxyisobutylisonitrile on the FDXR and XPA genes expression in human peripheral blood lymphocytes[J]. Asia Ocean J Nucl Med Biol, 2018, 6(1):32-40.;
[19] O'BRIEN G, CRUZ-GARCIA L, MAJEWSKI M, et al. FDXR is a biomarker of radiation exposure in vivo[J]. Sci Rep, 2018, 8(1):684.;
[20] PAUL S, BARKER C A, TURNER H C, et al. Prediction of in vivo radiation dose status in radiotherapy patients using ex vivo and in vivo gene expression signatures[J]. Radiat Res, 2011, 175(3):257-265.;
[21] KIM S J, DIX D J, THOMPSON K E, et al. Effects of storage, RNA extraction, genechip type, and donor sex on gene expression profiling of human whole blood[J]. Clin Chem, 2007, 53(6):1038-1045.;
[22] KOTURBASH I, KUTANZI K, HENDRICKSON K, et al. Radiation-induced bystander effects in vivo are sex specific[J]. Mutat Res Mol Mech Mutagen, 2008, 642(1/2):28-36.;
[23] RAICHE J, RODRIGUEZ-JUAREZ R, POGRIBNY I, et al. Sex- and tissue-specific expression of maintenance and de novo DNA methyltransferases upon low dose X-irradiation in mice[J]. Biochem Biophys Res Commun, 2004, 325(1):39-47.;
[24] TAVAKOLI H, MANOOCHEHRI M, MODARRES MOSALLA S M, et al. Dose-dependent and gender-related radiation-induced transcription alterations of Gadd45a and Ier5 in human lymphocytes exposed to gamma ray emitted by (60)Co[J]. Radiat Prot Dosimetry, 2013, 154(1):37-44.;
[25] ABEND M, BADIE C, QUINTENS R, et al. Examining radiation-induced in vivo and in vitro gene expression changes of the peripheral blood in different laboratories for biodosimetry purposes:first RENEB gene expression study[J]. Radiat Res, 2016, 185(2):109-123.;
[24] BADIE C, HESS J, ZITZELSBERGER H, et al. Established and emerging biomarkers of radiation exposure[J]. Clin Oncol (R Coll Radiol), 2016, 28(10):619-621.;
[26] BADIE C, KABACIK S, BALAGURUNATHAN Y, et al. Laboratory intercomparison of gene expression assays[J]. Radiat Res, 2013, 180(2):138-148.;
[27] KAJIMURA J, LYNCH H E, GEYER S, et al. Radiation- and age-associated changes in peripheral blood dendritic cell populations among aging atomic bomb survivors in Japan[J]. Radiat Res, 2018, 189(1):84-94.

性别和年龄对⁶⁰Co γ射线照射离体人外周血辐射敏感基因mRNA表达的影响

Effects of gender and age on expression of radiation-responsive genes in irradiated human peripheral blood samples

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	向嘉琪, 孙佳丽, 王成芳, 刘青杰, 田梅. ⁶⁰Co γ射线全身照射大鼠尿液的非标记定量蛋白质组学分析[J]. 癌变·畸变·突变, 2021, 33(3): 172-177,192.
[2]	陆雪, 田雪蕾, 赵骅, 蔡恬静, 田梅, 刘青杰. 人外周血淋巴细胞微核分析用于估算离体模拟局部照射剂量的研究[J]. 癌变·畸变·突变, 2021, 33(3): 193-196.
[3]	赵骅, 陆雪, 蔡恬静, 田梅, 刘青杰. 年龄和性别对正常人外周血淋巴细胞核质桥自发率的影响[J]. 癌变·畸变·突变, 2021, 33(1): 48-52.
[4]	秦双建, 李柏茹, 蔡颖, 郑凯, 王冰玉, 李闰冰, 肖芳, 曾明, 徐新云. PM_2.5对L02肝细胞部分癌基因和凋亡相关基因表达的影响[J]. 癌变·畸变·突变, 2020, 32(4): 281-285.
[5]	赵骅, 陆雪, 蔡恬静, 李爽, 田梅, 刘青杰. 基于代谢组学方法筛选大鼠血浆辐射敏感代谢物[J]. 癌变·畸变·突变, 2020, 32(3): 166-170,176.
[6]	田雪蕾, 封江彬, 田梅, 刘青杰. 甲基化芯片检测电离辐射诱导人外周血淋巴细胞DNA甲基化水平的变化[J]. 癌变·畸变·突变, 2019, 31(6): 434-439.
[7]	赵吉, 刘文斌, 陈洪强, 刘晋祎, 杨惠芳, 曹佳. WFDC1基因在肝癌中的表达及其诊断和预后价值[J]. 癌变·畸变·突变, 2018, 30(4): 291-296.
[8]	高延晓, 田梅, 高刚, 刘建香. 降扎乡高氡温泉周围居民血浆中8-羟基脱氧鸟苷和硫氧还蛋白还原酶水平的研究[J]. 癌变·畸变·突变, 2018, 30(3): 226-229.
[9]	王利, 彭鹏, 徐新云, 袁建辉, 龙鼎新. DEHP对3β-羟类固醇脱氢酶表达水平的影响[J]. 癌变·畸变·突变, 2017, 29(6): 445-449.
[10]	曲功霖, 李辰, 邵帅, 王春燕, 齐雪松, 佟鹏, 李宁. 四君子汤对电离辐射损伤的防治作用[J]. 癌变·畸变·突变, 2017, 29(4): 295-299.
[11]	张忠新, 张睿凤, 张慧芳, 段志凯. 常用辐射生物剂量计的研究现状[J]. 癌变·畸变·突变, 2016, 28(4): 325-328.
[12]	杨英杰, 刘建香, 高刚. 电离辐射对小鼠外周血单核细胞亚群的影响[J]. 癌变·畸变·突变, 2016, 28(4): 298-301.
[13]	许文黎, 岳娟, 袁慧, 黄立群, 王新钢, 王永丽, 闻建华. 氮氧自由基在辐射防护中的应用[J]. 癌变·畸变·突变, 2015, 27(6): 490-492.
[14]	姚欣雅, 赵敏娴, 曹正颖, 王灿楠. 结合体质量生长函数的幼年大鼠毒死蜱经口暴露PBTK/TD模型的研究[J]. 癌变·畸变·突变, 2015, 27(4): 249-259.
[15]	董小梅, 王治, 张国伟, 董建云, 周妮娅, 凌曦, 刘晋祎, 曹佳, 张丽龙, 敖琳. 低剂量工业射线探伤工人职业暴露的遗传损伤效应[J]. 癌变·畸变·突变, 2015, 27(2): 101-105.