梁春柳;朱江波;朱玉平;姚朗;张天宝;

• 1:南方医科大学公共卫生与热带医学学院毒理学系
• 2:第二军医大学卫生毒理学教研室

摘要(Abstract)：

为揭示纳米氧化锌(ZnO)遗传毒作用特征,以便为纳米材料的安全性评价提供科学依据,利用胞质分裂阻滞微核细胞组学实验和碱性彗星实验比较了纳米和微米尺度ZnO的遗传毒性。结果显示:①微米尺度ZnO在0.02～2.5μg·mL-1剂量下对微核、核质桥、核芽和核分裂指数(nucleus divided index,NDI)均无显著诱导作用(P>0.05);而纳米尺度ZnO在>0.5μg·mL-1剂量时可显著诱导细胞产生总微核、Ⅰ型微核和核芽(P<0.05),且均存在一定的剂量-效应关系,剂量为2.5μg·mL-1时,细胞的Ⅱ型微核数、核质桥数和NDI与对照组相比,也呈现出显著差异(P<0.05)。②剂量为2.5μg·mL-1时,处理9、18和24h后,与对照组相比,微米ZnO处理组中细胞各项指标的差异均无统计学意义(P>0.05),而纳米ZnO处理组中总微核数、Ⅰ型微核数和核质桥数具有时间-效应关系。③纳米ZnO在0.5μg·mL-1剂量时可诱导DNA损伤,而微米ZnO在2.5μg·mL-1剂量时才产生损伤效应。研究表明,纳米和微米尺度ZnO在遗传毒作用性质和毒性强弱方面均存在明显差异,纳米ZnO会诱导Ⅰ型、Ⅱ型微核、核芽和核质桥的产生以及DNA损伤,而微米ZnO仅在高剂量时会诱导DNA损伤。

关键词(KeyWords)： 纳米氧化锌;微米氧化锌;彗星实验;微核;核质桥;核芽

Abstract:

Keywords:

基金项目(Foundation): 国家重大科学计划子课题(2006CB932505);; 上海市科委纳米专项基金(0752nm020)

作者(Author): 梁春柳;朱江波;朱玉平;姚朗;张天宝;

Email:

参考文献(References)：

• [1]Hagens W I,Oomen A G,de Jong W H,et al.What do we(need to)know about the kinetic properties of nanoparticles in the body?[J].Regulatory Toxicology and Pharmacology,2007,49(3):217-229
• [2]Kurath M,Maasen S.Toxicology as a nanoscience?—Disciplinary identities reconsidered[J].Particle and Fibre Toxicology,2006,3(1):6
• [3]Lewinski N,Colvin V,Drezek R.Cytotoxicity of nanoparticles[J].Small,2008,4(1):26-49
• [4]Adams L K,Lyon D Y,Alvarez P J.Comparative eco-toxicity of nanoscale TiO2,SiO2,and ZnO water suspensions[J].Water Research,2006,40(19):3527-3532
• [5]Ramakrishna G,Gosh H N.Effect of particle size on the reactivity of quantum size ZnO nanoparticles and chargetransfer dynamics with adsorbed catechols[J].Langmuir,2003,19(7):3006-3012
• [6]Ding Y,Wang Z L.Structure analysis of nanowires and nanobelts by transmission electron microscopy[J].Journal of Physical Chemistry B,2004,108(33):1228012291
• [7]Zhu B L,Xie C S,Zeng D W,et al.Investigation of gas sensitivity of Sb-doped ZnO nanoparticle[J].Materials Chemistry and Physics,2005,89(1):148-153
• [8]Huang G G,Wang C T,Tang H T,et al.ZnO nanoparticle-modified infrared internal reflection elements for selective detection of volatile organic compounds[J].Analytical Chemistry,2006,78(7):2397-2404
• [9]Kasemets K,Ivask A,Dubourguier H,et al.Toxicity of nanoparticles of ZnO,CuO and TiO2to yeast Saccharomyces cerevisiae[J].Toxicology in Vitro,2009,23(6):1116-1122
• [10]Hu C W,Li M,Cui Y B,et al.Toxicological effects of TiO2and ZnO nanoparticles in soil on earthworm Eisenia fetida[J].Soil Biology and Biochemistry,2010,42(4):586-591
• [11]Bai W,Zhang Z Y,Tian W J,et al.Toxicity of zinc oxide nanoparticles to zebrafish embryo:A physicochemical study of toxicity mechanism[J].Journal of Nanoparticle Research,2010,12(5):1645-1654
• [12]Mortimer M,Kasemets K,Kahru A.Toxicity of ZnO and CuO nanoparticles to ciliated protozoa Tetrahymena thermophila[J].Toxicology,2010,269(2-3):182-189
• [13]Fenech M.Cytokinesis-block micronucleus cytome assay[J].Nature Protocols,2007,2(5):1084-1104
• [14]Hashimoto K,Nakajima Y,Matsumura S,et al.An in vitro micronucleus assay with size-classified micronucleus counting to discriminate aneugens from clastogens[J].Toxicology in Vitro,2010,24(1):208-216
• [15]Singh N P,McCoy M T,Tice R R,et al.A simple technique for quantitation of low levels of DNA damage in individual cells[J].Experimental Cell Research,1998,175(1):184-191
• [16]Tice R R,Agurell E,Anderson D,et al.Single cell gel/comet assay:Guidelines for in vitro and in vivo genetic toxicology testing[J].Environmental and Molecular Mutagenesis,2000,35(1):206-221
• [17]Fenech M.Cytokinesis-block micronucleus assay evolves into a"cytome"assay of chromosomal instability,mitotic dysfunction and cell death[J].Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis,2006,600(1-2):58-66
• [18]Wu J,Lyons G H,Graham R D,et al.The effect of selenium,as selenomethionine,on genome stability and cytotoxicity in human lymphocytes measured using the cytokinesis-block micronucleus cytome assay[J].Mutagenesis,2009,24(3):225-232
• [19]Dufour E K,Kumaravel T,Nohynek G J,et al.Clastogenicity,photo-clastogenicity or pseudo-photo-clastogenicity:Genotoxic effects of zinc oxide in the dark,in preirradiated or simultaneously irradiated Chinese hamster ovary cells[J].Mutation Research/Genetic Toxicology and Environmental Mutagenesis,2006,607(2):215224
• [20]Lin W S,Xu Y,Huang C C,et al.Toxicity of nanoand micro-sized ZnO particles in human lung epithelial cells[J].Journal of Nanoparticle Research,2009,11(1):25-39
• [21]洪丽玲.两种纳米与常规材料DNA损伤和亚慢性毒性的比较研究[D].上海:第二军医大学,2011:716Hong L L.Comparative study on DNA damage and subchronic toxicity caused by two kinds nano-and microscale material[D].Shanghai:The Second Military Medical University,2011:7-16(in Chinese)
• [22]Yin H,Casey P S,McCall M J,et al.Effects of surface chemistry on cytotoxicity,genotoxicity,and the generation of reactive oxygen species induced by ZnO nanoparticles[J].Langmuir,2010,26(19):15399-15408
• [23]SCCNFP.The Scientific Committee on Cosmetic Products and Non-Food Products Intended for Consumers,Opinion Concerning Zinc Oxide(Colipa no S76),Adopted by the SCCNFP during the24th Plenary Meeting of24-25June2003(SCCNFP/0649/03)[R/OL].(2003-0624)[2011-08-20].http://ec.europa.eu/health/ph risk/committees/sccp/documents/out222en.pdf
• [24]Borm P J.Particle toxicology:From coal mining to nanotechnology[J].Inhalation Toxicology,2002,14(3):311-324
• [25]曲秋莲,张英鸽,杨留中,等.纳米活性炭吸附丝裂霉素C腹腔化疗的实验研究[J].中华肿瘤杂志,2006,28(4):257-260Qu Q L,Zhang Y G,Yang L Z,et al.Intraperitoneal chemotherapy with mitomycin C bound to activated carbon nanoparticles for nude mice bearing human gastric carcinoma[J].Chinese Journal of Oncology,2006,28(4):257-260(in Chinese)