崔燕;白承连;徐涛;王晓彤;陈元红;靳大庆;

• 1:温州医学院水域科学与环境生态研究所 浙江省模式生物技术与应用重点实验室

摘要(Abstract)：

全氟辛酸(PFOA)是一种分布广泛的环境持久性有机污染物,在野生动物与人体内普遍被检出。目前PFOA发育毒性的特点和机制尚未阐明,已有的研究显示,PFOA毒性与受试物种及性别密切相关。因此,利用不同物种进行PFOA毒性研究对阐明其毒性机制十分重要。本研究选用了斑马鱼这种理想的脊椎动物模型,考察了PFOA暴露对其胚胎发育的自主运动、心跳、行为、细胞凋亡和DNA损伤的影响。研究发现,始于6hpf的PFOA暴露会导致斑马鱼胚胎自主运动异常,心率降低,且具有一定的剂量依赖性;6～24hpf的高浓度的PFOA暴露(>414.0mg·L-1)会导致胚胎发生显著的细胞凋亡,凋亡主要出现在眼部、头部、心脏和尾部。较高浓度的PFOA暴露(165.6mg·L-1)会使仔鱼的光刺激应激行为模式发生变化。此外,PFOA暴露会致使斑马鱼发生DNA损伤,且损伤程度随PFOA浓度的升高而加重,表明PFOA具有一定的基因毒性。上述结果表明,PFOA对斑马鱼胚胎具有发育毒性,具体表现为自主运动异常,心率降低和行为反应能力变弱,同时伴随畸形、细胞凋亡和DNA损伤。

关键词(KeyWords)： 全氟辛酸(PFOA);斑马鱼胚胎;发育毒性;行为反应;DNA损伤

Abstract:

Keywords:

基金项目(Foundation): 浙江省教育厅科研计划项目(Y201010056);; 温州市科技局国际合作项目(H20100062);; 浙江省自然科学基金一般项目(Y2110659);; 国家环保公益性行业科研专项(200909089)

作者(Author): 崔燕;白承连;徐涛;王晓彤;陈元红;靳大庆;

Email:

参考文献(References)：

• [1]3M Company.Sulfonated Perfluorochemicals in the Environment:Sources,Dispersion,Fate and Effects.US EPA OPPT AR-226-0620[R].Saint Paul:3M Company,2000
• [2]Jensen A A,Leffers H.Emerging endocrine disrupters:Perfluoroalkylated substances[J].International Journal of Andrology,2008,31(2):161-169
• [3]Olsen G W,Burris J M,Ehresman D J,et al.Half-life of serum elimination of perfluorooctanesulfonate,perfluorohexanesulfonate,and perfluorooctanoate in retired fluorochemical production workers[J].Environmental Health Perspectives,2007,115(9):1298-1305
• [4]Wei Y,Liu Y,Wang J,et al.Toxicogenomic analysis of the hepatic effects of perfluorooctanoic acid on rare minnows(Gobiocypris rarus)[J].Toxicology and Applied Pharmacology,2008,226(3):285-297
• [5]Haughom B,Spydevold.The mechanism underlying the hypolipemic effect of perfluorooctanoic acid(PFOA),perfluorooctane sulphonic acid(PFOSA)and clofibric acid[J].Biochimica et Biophysica Acta(BBA)-Lipids and Lipid Metabolism,1992,1128(1):65-72
• [6]Lau C,Anitole K,Hodes C,et al.Perfluoroalkyl acids:A review of monitoring and toxicological findings[J].Toxicological Sciences,2007,99(2):366-394
• [7]Wolf C J,Takacs M L,Schmid J E,et al.Activation of mouse and human peroxisome proliferator—Activated receptor alpha by perfluoroalkyl acids of different functional groups and chain lengths[J].Toxicological Sciences,2008,106(1):162-171
• [8]Escher P,Wahli W.Peroxisome proliferator—Activated receptors:Insight into multiple cellular functions[J].Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis,2000,448(2):121138
• [9]Biegel L B,Hurtt M E,Frame S R,et al.Mechanisms of extrahepatic tumor induction by peroxisome proliferators in male CD rats[J].Toxicological Sciences,2001,60(1):44-55
• [10]Cook J C,Murray S M,Frame S R,et al.Induction of Leydig cell adenomas by ammonium perfluorooctanoate:A possible endocrine-related mechanism[J].Toxicology and Applied Pharmacology,1992,113(2):209-217
• [11]Lau C,Thibodeaux J R,Hanson R G,et al.Effects of perfluorooctanoic acid exposure during pregnancy in the mouse[J].Toxicological Sciences,2006,90(2):510-518
• [12]White S S,Calafat A M,Kuklenyik Z,et al.Gestational PFOA exposure of mice is associated with altered mammary gland development in dams and female offspring[J].Toxicological Sciences,2007,96(1):133-144
• [13]Johansson N,Fredriksson A,Eriksson P.Neonatal exposure to perfluorooctane sulfonate(PFOS)and perfluorooctanoic acid(PFOA)causes neurobehavioural defects in adult mice[J].Neurotoxicology,2008,29(1):160-169
• [14]Butenhoff J L,Kennedy G L,Frame S R,et al.The reproductive toxicology of ammonium perfluorooctanoate(APFO)in the rat[J].Toxicology,2004,196(1-2):95-116
• [15]Sohlenius A K,Andersson K,DePierre J W.The effects of perfluoro-octanoic acid on hepatic peroxisome proliferation and related parameters show no sex-related differences in mice[J].Biochemical Journal,1992,285(3):779783
• [16]Peterson R T,Nass R,Boyd W A,et al.Use of nonmammalian alternative models for neurotoxicological study [J].Neurotoxicology,2008,29(3):546-555
• [17]Westerfield M.The Zebrafish Book:A Guide for the Laboratory Use of Zebrafish(Danio Rerio)[M].3rd Ed.Eugene:University of Oregon Press,1995:267-272
• [18]Kimmel C B,Ballard W W,Kimmel S R,et al.Stages of embryonic development of the zebrafish[J].Developmental Dynamics,1995,203(3):253-310
• [19]Usenko C Y,Harper S L,Tanguay R L.In vivo evaluation of carbon fullerene toxicity using embryonic zebrafish[J].Carbon,2007,45(9):1891-1898
• [20]Jarvis R B,Knowles J F.DNA damage in zebrafish larvae induced by exposure to low-dose rateγ-radiation:Detection by the alkaline comet assay[J].Mutation Research/Genetic Toxicology and Environmental Mutagenesis,2003,541(1-2):63-69
• [21]Johansson N,Eriksson P,Viberg H.Neonatal exposure to PFOS and PFOA in mice results in changes in proteins which are important for neuronal growth and synaptogenesis in the developing brain[J].Toxicological Sciences,2009,108(2):412-418
• [22]Saint-Amant L,Drapeau P.Time course of the development of motor behaviors in the zebrafish embryo[J].Journal of Neurobiology,1998,37(4):622-632
• [23]Panaretakis T,Shabalina I G,Grandér D,et al.Reactive oxygen species and mitochondria mediate the induction of apoptosis in human hepatoma HepG2cells by the rodent peroxisome proliferator and hepatocarcinogen,perfluorooctanoic acid[J].Toxicology and Applied Pharmacology,2001,173(1):56-64
• [24]Liu C,Yu K,Shi X,et al.Induction of oxidative stress and apoptosis by PFOS and PFOA in primary cultured hepatocytes of freshwater tilapia(Oreochromis niloticus)[J].Aquatic Toxicology,2007,82(2):135-143
• [25]Fairbairn D W,Olive P L,O'Neill K L.The comet assay:A comprehensive review[J].Mutation Research/Reviews in Genetic Toxicology,1995,339(1):37-59
• [26]Yao X,Zhong L.Genotoxic risk and oxidative DNA damage in HepG2cells exposed to perfluorooctanoic acid[J].Mutation Research/Genetic Toxicology and Environmental Mutagenesis,2005,587(1-2):38-44
• [27]Antkiewicz D S,Burns C G,Carney S A,et al.Heart malformation is an early response to TCDD in embryonic zebrafish[J].Toxicological Sciences,2005,84(2):368-377
• [28]Incardona J P,Collier T K,Scholz N L.Defects in cardiac function precede morphological abnormalities in fish embryos exposed to polycyclic aromatic hydrocarbons[J].Toxicology and Applied Pharmacology,2004,196(2):191-205
• [29]Yamauchi M,Kim E Y,Iwata H,et al.Molecular characterization of the aryl hydrocarbon receptors(AHR1and AHR2)from red seabream(Pagrus major)[J].Comparative Biochemistry and Physiology Part C:Toxicology&Pharmacology,2005,141(2):177-187
• [30]Hurd M W,Cahill G M.Entraining signals initiate behavioral circadian rhythmicity in larval zebrafish[J].Journal of Biological Rhythms,2002,17(4):307-314
• [31]MacPhail R C,Brooks J,Hunter D L,et al.Locomotion in larval zebrafish:Influence of time of day,lighting and ethanol[J].Neurotoxicology,2009,30(1):52-58
• [32]Huang H,Huang C,Wang L,et al.Toxicity,uptake kinetics and behavior assessment in zebrafish embryos following exposure to perfluorooctanesulphonicacid(PFOS)[J].Aquatic Toxicology,2010,98(2):139-147