碳纳米管生殖毒性及其毒作用机制研究进展
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摘要
随着碳纳米管(carbon nanotubes,CNTs)在各个领域应用的增加,人们接触到CNTs的几率也随之增加,越来越多的人开始关注CNTs对于人体是否具有毒性及其毒性的大小,近些年的体内和体外研究显示,CNTs可对生物体(如小鼠、斑马鱼、赤子爱胜蚓等)生殖系统产生毒性并遗传给后代,影响后代生长发育。本综述主要从CNTs种类、官能化和CNTs悬浮液中团聚体尺寸及所含杂质3个方面探讨CNTs的生殖毒性及毒作用机制,以及影响其毒性及毒作用机制的因素,从而为CNTs更加安全有效的应用提供依据。
With the increasing application of carbon nanotubes(CNTs) in various fields, the probability of people exposed to CNTs has been increasing as well. More and more people are paying attention to the fact whether CNTs are toxic to human body or not, and the severity of their toxicity. Recently, available in vivo and in vitro studies have shown that CNTs can cause toxic effects in the reproductive system of several organisms(such as mice, zebrafish, Eisenia foetida, etc.) and affect the offspring, resulting in the impairments of the growth and development of offspring. This review mainly discusses the reproductive toxicity of CNTs and their toxic mechanism from three aspects, which are CNTs species, functionalization, aggregate size and impurities in CNTs suspension. The factors influencing the toxicity of CNTs and their toxic mechanism has been discussed as well in order to provide a usefulinformation for the application of carbon nanotubes in a more safe and effective way.
With the increasing application of carbon nanotubes(CNTs) in various fields, the probability of people exposed to CNTs has been increasing as well. More and more people are paying attention to the fact whether CNTs are toxic to human body or not, and the severity of their toxicity. Recently, available in vivo and in vitro studies have shown that CNTs can cause toxic effects in the reproductive system of several organisms(such as mice, zebrafish, Eisenia foetida, etc.) and affect the offspring, resulting in the impairments of the growth and development of offspring. This review mainly discusses the reproductive toxicity of CNTs and their toxic mechanism from three aspects, which are CNTs species, functionalization, aggregate size and impurities in CNTs suspension. The factors influencing the toxicity of CNTs and their toxic mechanism has been discussed as well in order to provide a usefulinformation for the application of carbon nanotubes in a more safe and effective way.
引文
[1]张超星,边文越,王海名,等.世界主要国家纳米科技发展前瞻/部署分析研究[J].中国科学院院刊, 2017, 32(10):1142-1149Zhang C X, Bian W Y, Wang H M, et al. Analysis of nanoscience and technology plans of main countries[J].Bulletin of Chinese Academy of Sciences, 2017, 32(10):1142-1149(in Chinese)
[2]陈帅超,罗健林,李秋义,等.碳纳米管功能化修饰及其应用性能研究综述[J].功能材料, 2017, 48(12):12030-12035Chen S C, Luo J L, Li Q Y, et al. Research progress on CNT functionalization and its applications[J]. Journal of Functional Materials, 2017, 48(12):12030-12035(in Chinese)
[3] Zhang L D. Nanomaterials and nanostructures[J]. Chinese Academy of Sciences, 2001, 16(6):444-445
[4] Zhou Z F, Liu X F, Wu W, et al. Effective nerve cell modulation by electrical stimulation of carbon nanotube embedded conductive polymeric scaffolds[J]. Biomaterials Science, 2018, 9(6):2375-2385
[5]蒋爱华,陈瑞,白茹,等.碳纳米管及其复合材料在神经系统中的应用研究进展[J].生物物理学报, 2012, 28(6):457-468Jiang A H, Chen R, Bai R, et al. Research progress on application of carbon nanotubes and related nanocomposites in nervous systems[J]. Acta Biophysica Sinica, 2012, 28(6):457-468(in Chinese)
[6] Azqhandi M H A, Farahani B V, Dehghani N. Encapsula-tion of methotrexate and cyclophosphamide in interpolymer complexes formed between poly acrylic acid and poly ethylene glycol on multi-walled carbon nanotubes as drug delivery systems[J]. Materials Science&Engineering C-Materials for Biological Applications, 2017, 79(10):841-847
[7] Iijima S. Helical microtubles of graphitic carbon[J]. Nature, 1991, 354:56-58
[8] Oner D, Ghosh M, Bove H, et al. Differences in MWCNT-and SWCNT-induced DNA methylation alterations in association with the nuclear deposition[J]. Particle and Fibre Toxicology, 2018, 15(1):11
[9] Ventura C, Sousa-Uva A, Lavinha J, et al. Conventional and novel“omics”-based approaches to the study of carbon nanotubes pulmonary toxicity[J]. Environmental and Molecular Mutagenesis, 2018, 59(4):334-362
[10]徐诚. DNA损伤修复基因Xrcc1和代表性纳米材料对雄性生殖系统的影响及机制研究[D].南京:南京医科大学, 2017:56-68Xu C. Roles and molecular mechanisms of DNA damage repairgene Xrcc1 and selected nanometer materials on male reproductive system[D]. Nanjing:Nanjing Medical University, 2017:56-68(in Chinese)
[11] Ivani S, Karimi I, Tabatabaei S R, et al. Effects of prenatal exposure to single-wall carbon nanotubes on reproductive performance and neurodevelopment in mice[J]. Toxicology and Industrial Health, 2016, 32(7):1293-1301
[12] Hougaard K S, Jackson P, Kyjovska Z O, et al. Effects of lung exposure to carbon nanotubes on female fertility and pregnancy. A study in mice[J]. Eproductive Toxicology,2013, 41:86-97
[13] Arndt D A, Chen J, Moua M, et al. Multigeneration impacts on Daphnia magna of carbon nanomaterials with differing core structures and functionalizations[J]. Environmental Toxicology and Chemistry, 2014, 33(3):541-547
[14] Campagnolo L, Massimiani M, Palmieri G, et al. Biodistribution and toxicity of pegylated single wall carbon nanotubes in pregnant mice[J]. Particle and Fibre Toxicology, 2013, 10:21
[15] Aminzadeh Z, Jamalan M, Chupani L, et al. In vitro reprotoxicity of carboxyl-functionalised single-and multiwalled carbon nanotubes on human spermatozoa[J]. Andrologia, 2017, 49(9):e12741
[16] Agarwal A, Hamada A, Esteves S C. Insight into oxidative stress in varicocele-associated male infertility:Part 1[J]. Nature Reviews Urology, 2012, 9(12):678-690
[17] Bai Y, Zhang Y, Zhang J, et al. Repeated administrations of carbon nanotubes in male mice cause reversible testis damage without affecting fertility[J]. Nature Nanotechnology, 2010, 5(9):683-689
[18]诺娃.基于秀丽线虫的多壁碳纳米管毒性效应及mi RNA分子调控研究[D].南京:东南大学, 2014:39-64Abdelli Nouara. Toxicity of multi-walled carbon nanotubes on Caenorhabditis elegans and the related micro RNAs control[D]. Nanjing:Southeast University, 2014:39-64(in Chinese)
[19] Cheng J, Flahaut E, Cheng S H. Effect of carbon nanotubes on developing zebrafish(Danio rerio)embryos[J].Environmental Toxicology and Chemistry, 2007, 26(4):708-716
[20] Huang X, Zhang F, Sun X, et al. The genotype-dependent influence of functionalized multiwalled carbon nanotubes on fetal development[J]. Biomaterials, 2014, 35(2):856-865
[21]嵇伏年.基于蚯蚓体腔细胞的碳纳米管和五氯酚钠复合毒性效应研究[D].南京:南京大学, 2015:12-19Ji F N. Study of CNTs, PCP-Na and their complex toxic effect based on earthworm coelomocytes[D]. Nanjing:Nanjing University, 2015:12-19(in Chinese)
[22]熊楠,姚小珊,周秀花,等.环境中五氯酚对水生生物的毒理学研究进展[J].武汉工程大学学报, 2018, 40(2):119-126Xiong N, Yao X S, Zhou X H, et al. Recent research progress in toxicological effects of pentachlorophenol on aquatic organisms[J]. Journal of Wuhan Institute of Technology, 2018, 40(2):119-126(in Chinese)
[23]分析测试学报编辑部采编.中科院生态环境研究中心在碳纳米管毒理机制方面取得系列进展[J].分析测试学报, 2017, 36(8):1060
[24] Lindberg H K, Falck G C M, Suhonen S, et al. Genotoxicity of nanomaterials:DNA damage and micronuclei induced by carbon nanotubes and graphite nanofibers in human bronchial epithelial cell in vitro[J]. Toxicology Letters, 2009, 186(3):166-173
[25] Zhang X P, Liu F, Cheng Z, et al. Cell fate decision mediated by p53 pulses[J]. Proceedings of the National Academy of Sciences of the United States of America, 2009,106(30):12245-12250
[26] Purvis J E, Karhohs K W, Mock C, et al. P53 dynamics control cell fate[J]. Science, 2012, 336(6087):1440-1444
[27] Zhang X P, Liu F, Cheng Z, et al. Two-phase dynamics of p53 in the DNA damage response[J]. Proceedings of the National Academy of Sciences of the United States of America, 2011, 108(22):8990-8995
[28] Zinkel S, Gross A, Yang E. BCL2 family in DNA damageand cell cycle control[J]. Cell Death and Differentiation,2006, 13(8):1351-1359
[29] Mirzayans R, Andrais B, Scott A, et al. New insights into p53 signaling and cancer cell response to DNA damage:Implications for cancer therapy[J]. Journal of Biomedicine&Biotechnology, 2012, 2012:170325
[30] Yamaguchi Y, Shinotsuka N, Nonomura K. Live imaging of apoptosis in a novel transgenic mouse highlights its role inneural tube closure[J]. Journal of Cell Biology,2011, 195(6):1047-1060
[31] Ma S, Charron J, Erikson R L. Role of Plk2(Snk)in mouse development and cell proliferation[J]. Molecular and Cellular Biology, 2003, 23(19):6936-6943
[32]杨伯清.地塞米松和碳纳米管对卵巢颗粒细胞孕酮分泌的影响及分子机制初步研究[D].北京:北京协和医学院, 2012:36-41Yang B Q. Effects of dexamethasone and carbon nanotubes on progesterone secretion of ovarian granulosa cells and preliminary study on its molecular mechanism[D].Beijing:Peking Union Medical College, 2012:36-41(in Chinese)
[33]白预弘.功能化多壁碳纳米管对小鼠生殖毒性的研究[D].济南:山东大学, 2011:33-67Bai Y H. Study on reproductive toxicity of functionalized multi-walled carbon nanotubes in mice[D]. Jinan:Shandong University, 2011:33-67(in Chinese)
[34]孙建玲.多壁碳纳米管对雌性小鼠生殖系统影响的研究[D].济南:山东大学, 2013:21-49Sun J L. Investigation of female reproductive toxicity induced by multi-walled carbon nanotubes[D]. Jinan:Shandong University, 2013:21-49(in Chinese)
[35]王利鑫.多壁碳纳米管对人工模拟细胞膜和质膜囊泡的作用及过程[D].济南:山东大学, 2016:35-44Wang L X. The effect and process of multi-walled carbon nanotubes on artificially simulated cell membrane and plasma membrane vesicle[D]. Jinan:Shandong University, 2016:35-44(in Chinese)
[36]李玲丽.纳米材料的生物响应、生物合成及利用[D].合肥:中国科学技术大学, 2017:1-11Li L L. Response of environmental organisms to nanomaterials and their biosynthesis and applications[D].Hefei:University of Science and Technology of China,2017:1-11(in Chinese)
[37] Ionit,M, CricL E, Voicu S I, et al. Synergistic effect of carbon nanotubes and graphene for high performance cellulose acetate membranes in biomedical applications[J].Carbohydrate Polymers, 2018, 183:50-61
[2]陈帅超,罗健林,李秋义,等.碳纳米管功能化修饰及其应用性能研究综述[J].功能材料, 2017, 48(12):12030-12035Chen S C, Luo J L, Li Q Y, et al. Research progress on CNT functionalization and its applications[J]. Journal of Functional Materials, 2017, 48(12):12030-12035(in Chinese)
[3] Zhang L D. Nanomaterials and nanostructures[J]. Chinese Academy of Sciences, 2001, 16(6):444-445
[4] Zhou Z F, Liu X F, Wu W, et al. Effective nerve cell modulation by electrical stimulation of carbon nanotube embedded conductive polymeric scaffolds[J]. Biomaterials Science, 2018, 9(6):2375-2385
[5]蒋爱华,陈瑞,白茹,等.碳纳米管及其复合材料在神经系统中的应用研究进展[J].生物物理学报, 2012, 28(6):457-468Jiang A H, Chen R, Bai R, et al. Research progress on application of carbon nanotubes and related nanocomposites in nervous systems[J]. Acta Biophysica Sinica, 2012, 28(6):457-468(in Chinese)
[6] Azqhandi M H A, Farahani B V, Dehghani N. Encapsula-tion of methotrexate and cyclophosphamide in interpolymer complexes formed between poly acrylic acid and poly ethylene glycol on multi-walled carbon nanotubes as drug delivery systems[J]. Materials Science&Engineering C-Materials for Biological Applications, 2017, 79(10):841-847
[7] Iijima S. Helical microtubles of graphitic carbon[J]. Nature, 1991, 354:56-58
[8] Oner D, Ghosh M, Bove H, et al. Differences in MWCNT-and SWCNT-induced DNA methylation alterations in association with the nuclear deposition[J]. Particle and Fibre Toxicology, 2018, 15(1):11
[9] Ventura C, Sousa-Uva A, Lavinha J, et al. Conventional and novel“omics”-based approaches to the study of carbon nanotubes pulmonary toxicity[J]. Environmental and Molecular Mutagenesis, 2018, 59(4):334-362
[10]徐诚. DNA损伤修复基因Xrcc1和代表性纳米材料对雄性生殖系统的影响及机制研究[D].南京:南京医科大学, 2017:56-68Xu C. Roles and molecular mechanisms of DNA damage repairgene Xrcc1 and selected nanometer materials on male reproductive system[D]. Nanjing:Nanjing Medical University, 2017:56-68(in Chinese)
[11] Ivani S, Karimi I, Tabatabaei S R, et al. Effects of prenatal exposure to single-wall carbon nanotubes on reproductive performance and neurodevelopment in mice[J]. Toxicology and Industrial Health, 2016, 32(7):1293-1301
[12] Hougaard K S, Jackson P, Kyjovska Z O, et al. Effects of lung exposure to carbon nanotubes on female fertility and pregnancy. A study in mice[J]. Eproductive Toxicology,2013, 41:86-97
[13] Arndt D A, Chen J, Moua M, et al. Multigeneration impacts on Daphnia magna of carbon nanomaterials with differing core structures and functionalizations[J]. Environmental Toxicology and Chemistry, 2014, 33(3):541-547
[14] Campagnolo L, Massimiani M, Palmieri G, et al. Biodistribution and toxicity of pegylated single wall carbon nanotubes in pregnant mice[J]. Particle and Fibre Toxicology, 2013, 10:21
[15] Aminzadeh Z, Jamalan M, Chupani L, et al. In vitro reprotoxicity of carboxyl-functionalised single-and multiwalled carbon nanotubes on human spermatozoa[J]. Andrologia, 2017, 49(9):e12741
[16] Agarwal A, Hamada A, Esteves S C. Insight into oxidative stress in varicocele-associated male infertility:Part 1[J]. Nature Reviews Urology, 2012, 9(12):678-690
[17] Bai Y, Zhang Y, Zhang J, et al. Repeated administrations of carbon nanotubes in male mice cause reversible testis damage without affecting fertility[J]. Nature Nanotechnology, 2010, 5(9):683-689
[18]诺娃.基于秀丽线虫的多壁碳纳米管毒性效应及mi RNA分子调控研究[D].南京:东南大学, 2014:39-64Abdelli Nouara. Toxicity of multi-walled carbon nanotubes on Caenorhabditis elegans and the related micro RNAs control[D]. Nanjing:Southeast University, 2014:39-64(in Chinese)
[19] Cheng J, Flahaut E, Cheng S H. Effect of carbon nanotubes on developing zebrafish(Danio rerio)embryos[J].Environmental Toxicology and Chemistry, 2007, 26(4):708-716
[20] Huang X, Zhang F, Sun X, et al. The genotype-dependent influence of functionalized multiwalled carbon nanotubes on fetal development[J]. Biomaterials, 2014, 35(2):856-865
[21]嵇伏年.基于蚯蚓体腔细胞的碳纳米管和五氯酚钠复合毒性效应研究[D].南京:南京大学, 2015:12-19Ji F N. Study of CNTs, PCP-Na and their complex toxic effect based on earthworm coelomocytes[D]. Nanjing:Nanjing University, 2015:12-19(in Chinese)
[22]熊楠,姚小珊,周秀花,等.环境中五氯酚对水生生物的毒理学研究进展[J].武汉工程大学学报, 2018, 40(2):119-126Xiong N, Yao X S, Zhou X H, et al. Recent research progress in toxicological effects of pentachlorophenol on aquatic organisms[J]. Journal of Wuhan Institute of Technology, 2018, 40(2):119-126(in Chinese)
[23]分析测试学报编辑部采编.中科院生态环境研究中心在碳纳米管毒理机制方面取得系列进展[J].分析测试学报, 2017, 36(8):1060
[24] Lindberg H K, Falck G C M, Suhonen S, et al. Genotoxicity of nanomaterials:DNA damage and micronuclei induced by carbon nanotubes and graphite nanofibers in human bronchial epithelial cell in vitro[J]. Toxicology Letters, 2009, 186(3):166-173
[25] Zhang X P, Liu F, Cheng Z, et al. Cell fate decision mediated by p53 pulses[J]. Proceedings of the National Academy of Sciences of the United States of America, 2009,106(30):12245-12250
[26] Purvis J E, Karhohs K W, Mock C, et al. P53 dynamics control cell fate[J]. Science, 2012, 336(6087):1440-1444
[27] Zhang X P, Liu F, Cheng Z, et al. Two-phase dynamics of p53 in the DNA damage response[J]. Proceedings of the National Academy of Sciences of the United States of America, 2011, 108(22):8990-8995
[28] Zinkel S, Gross A, Yang E. BCL2 family in DNA damageand cell cycle control[J]. Cell Death and Differentiation,2006, 13(8):1351-1359
[29] Mirzayans R, Andrais B, Scott A, et al. New insights into p53 signaling and cancer cell response to DNA damage:Implications for cancer therapy[J]. Journal of Biomedicine&Biotechnology, 2012, 2012:170325
[30] Yamaguchi Y, Shinotsuka N, Nonomura K. Live imaging of apoptosis in a novel transgenic mouse highlights its role inneural tube closure[J]. Journal of Cell Biology,2011, 195(6):1047-1060
[31] Ma S, Charron J, Erikson R L. Role of Plk2(Snk)in mouse development and cell proliferation[J]. Molecular and Cellular Biology, 2003, 23(19):6936-6943
[32]杨伯清.地塞米松和碳纳米管对卵巢颗粒细胞孕酮分泌的影响及分子机制初步研究[D].北京:北京协和医学院, 2012:36-41Yang B Q. Effects of dexamethasone and carbon nanotubes on progesterone secretion of ovarian granulosa cells and preliminary study on its molecular mechanism[D].Beijing:Peking Union Medical College, 2012:36-41(in Chinese)
[33]白预弘.功能化多壁碳纳米管对小鼠生殖毒性的研究[D].济南:山东大学, 2011:33-67Bai Y H. Study on reproductive toxicity of functionalized multi-walled carbon nanotubes in mice[D]. Jinan:Shandong University, 2011:33-67(in Chinese)
[34]孙建玲.多壁碳纳米管对雌性小鼠生殖系统影响的研究[D].济南:山东大学, 2013:21-49Sun J L. Investigation of female reproductive toxicity induced by multi-walled carbon nanotubes[D]. Jinan:Shandong University, 2013:21-49(in Chinese)
[35]王利鑫.多壁碳纳米管对人工模拟细胞膜和质膜囊泡的作用及过程[D].济南:山东大学, 2016:35-44Wang L X. The effect and process of multi-walled carbon nanotubes on artificially simulated cell membrane and plasma membrane vesicle[D]. Jinan:Shandong University, 2016:35-44(in Chinese)
[36]李玲丽.纳米材料的生物响应、生物合成及利用[D].合肥:中国科学技术大学, 2017:1-11Li L L. Response of environmental organisms to nanomaterials and their biosynthesis and applications[D].Hefei:University of Science and Technology of China,2017:1-11(in Chinese)
[37] Ionit,M, CricL E, Voicu S I, et al. Synergistic effect of carbon nanotubes and graphene for high performance cellulose acetate membranes in biomedical applications[J].Carbohydrate Polymers, 2018, 183:50-61