摘要
硝基苯(Nitrobenzene,NB)的分子式为C6H5NO2,分子量为123.06,是重要的化工原料,广泛应用于国防、印染、塑料、农药和医药工业,全世界每年排入环境中的硝基苯类化合物约为1万吨,是环境中主要的有机污染物之一。NB具有弱致突变性,长期接触对人体及动植物危害极大,现已被我国国家环保局列为水中优先控制的有机污染物,美国环保局(EPA)也规定NB为环境中优先监测污染物。随着化工业的迅速发展,硝基苯越来越多地进入渔业水域,在我国松花江中游硝基苯检出率较高,过量的硝基苯排入水体,会引起水质恶化,影响鱼类的生存,破坏水生生态系统,还可以在生物体内富集,危害人类健康。
本文以NB为研究对象,采用实验室模拟胚胎孵化及单细胞凝胶电泳技术,研究了NB对鲢、鳙胚胎发育所产生的影响和NB对斑马鱼肝胰脏、肾脏、鱼鳍、精子细胞DNA损伤作用,并对NB的作用机理进行了初步探讨。研究结果表明:
1.暴露于不同浓度硝基苯处理组的鲢胚胎表现出与对照组不同的死亡率及畸形率,以及发育的延迟。随着硝基苯浓度的增加,鲢胚胎的死亡率及畸形率呈上升趋势,当暴露浓度>0.85 mg?L-1时,鲢胚胎的死亡率达到100 %。硝基苯浓度为0.017~0.425 mg?L-1时,胚胎发育分别延迟3~16 h,而暴露于浓度为0.85 mg?L-1以及1.7 mg?L-1中的鲢胚胎在32h全部死亡。
2.暴露于不同浓度硝基苯处理组的鳙胚胎表现出与对照组不同的死亡率及畸形率,以及发育的延迟。随着硝基苯浓度的增加,鳙胚胎的死亡率及畸形率呈上升趋势,当暴露浓度>0.85mg?L-1时,鳙胚胎的死亡率达到100%。硝基苯浓度为0.017~0.425 mg?L-1时,胚胎发育分别延迟4~8 h。而暴露于浓度为0.85 mg?L-1以及1.7 mg?L-1中的鳙胚胎在25 h全部死亡。
3.硝基苯在一定浓度范围内对斑马鱼肝胰脏(0.106~1.7 mg?L-1)、肾脏(0.017~1.7 mg?L-1)、鱼鳍(0.017~1.7 mg?L-1)、精子(0.106~1.7 mg?L-1)细胞DNA产生了损伤作用,且细胞的平均彗尾长度(损伤度)及受损率随硝基苯浓度的升高而升高,损伤细胞分布随着浓度的升高,由0、1级损伤细胞占优势转变为2、3级损伤细胞占优势。
综上所述,NB可以引起鲢、鳙胚胎发育的延迟,并可导致胚胎在发育中死亡和畸形的产生。对斑马鱼的肝胰脏、肾脏、鱼鳍、精子细胞也可引起DNA的损伤,表现出遗传毒性。
Nitrobenzene, C6H5NO2, is an important chemical raw material and widely used in national defense, dyeing and printing, plastics, pesticides and pharmaceutical industry. There is about 10,000 tons nitrobenzene compounds discharged into the environment each year in the world, is one of the major organic pollutants now. NB is weak mutagenicity that long-term exposure to humans and plants and animals will result in great harm. With the rapid development of the chemical industry, more and more nitrobenzene was discharged into the middle reaches of the Songhua River in China, cause deterioration of water quality and affect the aquatic ecosystems, also enriched in the organism and may be endanger to human health.
This paper selected contaminant nitrobenzene (NB) as resaerch object, use laboratory simulation of embryos hatching and single-cell gel electrophoresis technique, studied the effect of NB on the silver carp, bighead carp embryonic development and DNA damage of the zebrafish liver and pancreas, kidney, fin, sperm cell. Moreover, this paper tried to probe into the effect mechanism of NB. Which provided the basis for the fully estimate of ecological toxicology on aquatic organism. The results showed that:
1. Silver carp embryos that exposed to different concentrations of nitrobenzene compare to the control group showed different mortality and abnormality rate, and development was delayed. With increasing concentration of nitrobenzene, embryo mortality and abnormality rate upward trend, when exposed concentration> 0.85 mg?L-1, mortality reached 100%. embryonic development delayed for 3 to 16 h at the concentration of 0.017 ~ 0.425 mg?L-1, and embryos were all dead at 32 h exposure to the concentration of 0.85 mg?L-1 and 1.7 mg?L-1 .
2. Bighead carp embryos that exposed to different concentrations of nitrobenzene compare to the control group showed different mortality and deformity rate, and development was delayed too. With increasing concentration of nitrobenzene, embryo mortality and abnormality rate upward trend, when exposed concentration> 0.85 mg?L-1, mortality reached 100%. embryonic development delayed for 4 to 8 h at the concentration of 0.017 ~ 0.425 mg?L-1, and embryos were all dead at 25 h exposure to the concentration of 0.85 mg?L-1 and 1.7 mg?L-1 .
3. Certain concentration of nitrobenzene induced DNA damage on cell of zebrafish liver and pancreas (0.106 ~ 1.7 mg?L-1), kidney (0.017 ~ 1.7 mg?L-1), fins (0.017 ~ 1.7 mg?L-1), sperm (0.106 ~ 1.7 mg?L-1). Injured cells and the average tail length increased with the concentration of nitrobenzene. Distribution of cell changed with the increase of concentration, 0,1grade damage cell dominant into 2,3 grade damage cell dominant.
Sum up, NB can make silver, bighead carp embryonic development delay, and may result in the development of fetal death and abnormality fries. NB also induced DNA damage on the liver and pancreas, kidney, fin, sperm cells of Zebrafish, showed genetic toxicity.
引文
曹建萍.2007.硝基苯对鲫鱼肝脏的氧化损伤研究.东北师范大学硕士论文
长江水产研究所.1973.家鱼人工繁殖技术.中国农业出版社
程忆渤,张宗毅.1996.三硝基甲苯和2,4-二硝基甲苯对小鼠精子畸形的联合毒性研究.劳动医学,13(4):212~214
程倩.1999.硝基芳烃对隆线蚤的毒性作用及QSAR研究.辽宁师范大学学报(自然科学版),22(2): 148~152
郭永军,陈成勋,李占军等.2004.水温和盐度对鲤鱼(Cyprinus carpio)胚胎和前期仔鱼发育的影响.天津农学院学报,11(3):231~233
韩春华,王启恩,吴萍等.2001.硝基苯对肝癌细胞系的细胞毒性机制.中华预防医学杂志,35(1):48~50
李景舜,赵淑华,隧春生等.1994.硝基苯致鼠肝质过氧化.中华劳动卫生职业病杂志, 12(3):27~28
李思发等.1990.长江、珠江、黑龙江鲢、鳙草鱼种质资源研究.上海科学技术出版社
历以强,孙立伟,曲薨薨等.2004.氨基酚类化合物对鲤鱼(Cyprinus caprio)肾细胞遗传毒性的影响.环境科学研究,17(5):36~37
刘红玲,于红霞.2007.联苯胺类化合物对斑马鱼胚胎发育毒性的初步研究.生态毒理学报,2(1):95~98
刘淑芬,蒋湘宁,徐晓白等.1996.2-硝基芴的DNA加合物的研究.环境化学, 15(3):240~246
楼允东.1965.鱼类的孵化酶.动物学杂志,7(2):14~16
吕丹瑜,刘雅穷,刘宁等.2006.二甲苯对妊娠小鼠及胚胎发育的毒性作用.解剖学报,37(3):355~357
马德元,马文彦,刘哲生等.1998.急性苯的氨基、硝基化合物中毒临床分析(附69例报告).中华劳动卫生职业病杂志,14(5) 242~243
马汐平,付宝荣,刘洁等.1999.制药废水中硝基苯致突性的细菌检测试验.辽宁大学学报,26(2):175~178
沈洪艳,宋存义等.2007.3种硝基苯污染物对锦鲤鱼的急性毒性.农业环境科学学报,26 (增刊):63~ 67
沈惠麟,张金华.1998.间二硝基苯对大鼠肝脏氧化损伤的研究.中华劳动职业病杂志, 6(16):129~132
宋博,蔡志明,李欣等.2005.苯对人精子DNA损伤的影响.中华男科学杂志,11(1):53~55
王镜岩,朱圣庚,徐长法.2002.生物化学(第三版).高等教育出版社,P516
汪堃仁，薛绍白，柳惠图．1998.细胞生物学(第二版).高等教育出版社,p45~46
王民生,Shcmezer P.1996.碱性单细胞微量凝胶电泳测试技术简介.癌变.畸变.突变, 8(2):112~115
王启恩,王红兵,韩春华等.1998.间二硝基苯对肝细胞DNA的损伤及胆红素的抑制作用研究.职业医学,25(6):5~6
王天成,李宏,沈惠麟.1998.间二硝基苯染毒对大鼠血清生化指标的影响.中国工业医学杂志,11(5):271~273
王天成,张金华,马文军等.2007.间二硝基苯诱导大鼠肝细胞DNA氧化损伤.中国公共卫生,9(23):1108~1109
王武.2000.鱼类增养殖学.中国农业出版社, 469~479.
王新.2006.五氯硝基苯对雄性小鼠生殖系统毒性作用.东北师范大学硕士论文,26~27
王英彦,马玉琴,张月敬等.1992.用斑马鱼超弱光技术检测水体污染.环境科学,13(6):2~5
王阳峰,吕玉新.2004.用水生态毒理学方法评价13种硝基苯类化合物的急性毒性.新乡医学院学报,21(6):456~458
刑厚娟.2007.硝基苯对昆明小鼠亚急性毒性的研究.东北农业大学硕士论文,27~28
谢凤君,陈惠志,赵幼一.1992.斑马鱼在环境监测上的应用研究.中国环境监测,(4): 20~21
修瑞琴,高世荣,许永香等.1992.肼与苯肼对斑马鱼胚胎和仔鱼的毒性研究.环境科学.13(6):67~69
徐镜波,杨丽,赵立群.2005.间二硝基苯对小鼠皋丸生殖细胞DNA损伤作用的SCGE研究.东北师大学报自然科学版,37(3): l15~118
徐立红,张甬元,陈宜瑜.1995.分子生态毒理学研究进展及其在水环境保护中的意义.水生生物学报,19(2):171~185
薛良义,李卢,周济胜.2005.硝基苯和氯苯对卿鱼血细胞DNA损伤的研究.水利渔业,25(3):8~9
易伯鲁.1988.水利枢纽建设与渔业生态研究专集,葛洲坝水利枢纽与长江四大家鱼.湖北科技出版社
游学军,郑永华.2001.对氯硝基苯对草鱼种肝胰脏过氧化氢酶活性的影响.中国环境科学,14(4):79~82.
赵淑华,李景舜.2007.硝基苯对小鼠睾丸细胞酶的作用.环境与健康杂志,10(24):800~801
郑敏,朱琳.2005.五氯酚对斑马鱼胚胎的毒性效应研究.应用生态学报,16(10):1967~1971
钟麟等.1965.家鱼的生物学和人工繁殖.科学出版社.
Abdusamadov A.S..1987. Biology of white amur (Ctenopharyngodon idella),silver carp (Hypophthalmichthys molitrix),and bighead (Aristichthys nobilis),acclimatized in the Terek Region of the Caspian Basin.Journal of Ichthyology,26(4):41~49
Anderson D.,Yu T.W.,Mcgregor D.B..1998.Comet assay responses as indieators of carcinogen exposure.Mutagenesis,13(6):53~55
Angelis K.J.,Dusinska M.,Collins A.R..1999.Single cell gel electrophoresis: detection of DNA damage at different levels of sensitivity.Electrophoresis,20 (10):2133~2138
Auman H.J.,Yelon D.2004.Vertebrate organogenesis:getting the heart into shape.CurrBiol, 14(4):152~153
Bainter J.J.,Boos A.,Kroll K.L.2001.Neural induction takes a Transcriptional twist.DevDyn,222 (3):315~327
Banath J.P.,Fushiki M.,Olive P.L..1998.Rejoining of DNA single-and double-strand brekas in human White blood cells exposed to ionizing radiation.Int J Radiat Biol,73(6):649~660.
Bassett D.I.,Bryson-Richardson R.J.,Daggett D.F.,et al.2003. Dystrophinis requiredfor the formation of stablemuscle attachments in the zebrafish embryo. Development,130(23):5851~5860
Brownlie A.,Donovan A.,Pratt S.J.,et al.1998.Positional cloning of the zebrafish sauternes gene:a model for congenital sider oblasticanaemia.NatGenet,20(3):244~250
Carvan M.J.,Dalton T.P.,Stuart G.W.,et al.2000.Transgenic zebrafish as sentinels for aquatic pollution.Ann NYA cad Sci,919:133~147
Chang Y.F..1966.Culture of freshwater fish in China.In E.O. Gangstad,editor. 1980.Chinese fish culture.Report 1.Technical report A-79.Aquatic plant control research program.Washington,DC. U.S. Army Waterways Experiment Station (draft translated by T.S.Y. Koo,1980)
Chervinski J..1980.Note on the adaptability of big-head (Aristichthys nobilis) to various saline concentrations. Bamidgeh.32(1):27~29
Collazo A.,Fraser S.E.,and Mabee P.M..1994.A dual embryomic origin for vertebrate mechanoreceptor,.Science,264:426~430
Collins A.R.,Dobson V.L.,Dusinska M. et al.1997.The comet assay:what can it really tell us .Mutat Res,375 (2):183~193
Collins A.R.,Harrington V.,DrewJ.,et al.2003.Nutritional modulation of DNA repair in a human intervention study.Carcinogenesis,24 (3):511~512
Collins A.R.,Dusinska M.,Franklin M.,Somorovska M.,Petrovska H.,Duthie S.,Fillion L.,Pnaayiotidis M.,Raslova K.,Vaughan N..1997.Comet assay in human biomonitoring studies:relibaility,validation,and applications.Environ Mol Mutagen,30(2):139~146
Cook P. R.,Brazell A.,Jost E..1976.Characterization of nuelear sturetures containing superhelical DNA.J.Cell Sci,22(2):303~324.
Darland T.,Dowling J.E..2001.Behavioral screening for cocaine sensitivity in mutagenized zebrafish.Proc Natl Acad Sci ,98(20):11691~11696
Dincer Y.,Akcay T.,Ilkova H.,et al .2003.DNA damage and antioxidant defense in peripheral leukocytes of patients with Type I diabetes mellitus.Mutat Res ,527 (122) :49~55
Driever W.,Solnica-Krezel L.,Schier A.F.,et al.1996.A genetic Screen formutations affecting embryo genesisin zebrafish.Development,123:37~46
Driever W.,Stemple D.,Sehier A.,and Solniea-kiezel L..1994.Zebrafish:genetic tools for studying for vertebrate develoPlnent.Trends in Generies,10(5):152~159
Drummond I.A.,Majumdar A.,Hentschel H.,et al.1998.Early development of the zebrafish pronephros and analysis of mutations affecting pronephric function.Development,125(23):4655~4667
Deutc J.M..1988.The retical studies of DNA during gel elcetrophoresis.Science, 240(4854):922~924
Ensenbach U & Nagel R.1995.Toxicity of complex chemical mixtures:acute and long-term effects on different life stages of zebrafish.Ecotoxicol Env Saf,0:151~157
Elizondo M.R.,Arduini B.L.,Paulsen J.,et al.2005.Defective skeletogenesis with kidney stone formation in dwarf zebrafish mutant for trpm 7.Curr Biol,15(7):667~671
FAO.1972. Aquaculture development.FAO Aquaculture Bulletin, 4(4):7~11.
FAO.1980.Pond fish culture in China.Pearl River Fisheries Research Institute.China National Bureau of Aquatic Products.Ghangzhou.China.136 pp
Fan Z., editor.1990.The conservation atlas of China.Sponsored by NationalEnvironmental Protection Agency,compiled by Changchun Institute of Geography,Chinese Academy of Sciences.Science Press,Beijing.238 pp
Fermin A.C..1990.Sexual maturation of bighead carp,Aristichthys nobilis (Richardson),during high turbidity and seawater intrusion in Laguna de Bay,Philippines.Journal of Applied Ichthyology,6:129~135
Fernandez J.L.,Vazquez-Gundin F.,Rivero M.T.,et al.2001.DBD-fish on neutral comets:simultaneous analysis of DNA single- and double-strand breaks in individual cells.Exp Cell Res ,270 (1):102~109
Fleming A.,Sato M.,,Goldsmith P..2005. High-throughput in vivo screening for bone anabolic compounds with zebrafish.J Biomol Screen,10(8):823~831
Francesca M.,Antonietta M.,Marzia G..2006.DNA fragmentation and DNA repair synthesis induced in rat and human thyroid cells by chemicals carcinogenic to the rat thyroid.7(13):823~831
Freeze M.T.,Crawford.1983.Fall spawning of silver carp.Progressive Fish-Culturist,45:133
Froese R. and D. Pauly,editors.2004.FishBase,version 9/2004.World Wide Web electronic publication.
Fukuda K.,KikuchiY.2005.Endoderm development in vertebrates:Fate mapping,induction an dregional specification.Dev Growth Differ,47(6):343~355
Gahtan E.,Sankrithi N.,Campos J.B.,et al.1993.Evidence for a widespread brain sterm escape network in larvalfish.J Biotech adv,11:13~29
Garcia L.M.B.,Garcia C.M.H., Pineda A.F.S.,et al.1999. Survival and growth of bighead carp fry exposed to low salinities.Aquaculture International,7:241~250
Goldsmith P.,Harris W.A..2003.The zebrafish as a tool for understanding the biology of visual disorders.Semin Cell Dev Biol,14(1):11~18
Goldstein I.,Popoviei C..1960.Catalase and Peroxidase Changes in experimental Nitrobenzene, Poisoning.Med Lav,51:42~48
Gorbach E.I.,and M.L. Krykhtin.1989.Migration of the white amur, Ctenopharyngodon idella, and silver carp,Hypophthalmichthys molitrix,in the Amur River Basin.Journal of Ichthyology,28(4):47~53
Gulati-Leekha A.,Goldman D.A..2006.reporter-assisted mutagenesis screen using alpha1-tubulin-GFP transgenic zebrafishuncovers missteps during neuronal development and axonogenesis.Dev Biol,296(1):9~47
Haffter P.,Granato M.,Brand M., et al.1996.The identification of genes with unique and essential functions in the development of the zebrafish,Daniorerio.Development,123:1~36
Hallare A.V.,Pagulayan R.,Lacdan N.,et al.2005Assessing water quality in a tropical lake using biomarkersin zebrafish embryos : developmental toxicity and stress protein responses. Environ Monit Assess,104(1):171~187
Helok K.A.,Wilson E.T.,Creteko C.J.,and Grunwald D.J..1994.Contribution of early cell,to the fate map of the zebrafish gastrula.Science,265:517~520
Ignacio A.R.,Timothy L.,Hugh K.R.,et al.1995.Early metabolism changes during mdinitrobenzene neurotoxicity and the possible role of oxidative stress.Free Radical & medicine,18 (2):311~319
Jin S.W.,Beis D.,Mitchell T.,et al.2005.Cellular and molecular analyses of vasculartube and lumen formation in zebrafish.Development,132(23):5199~5209
Kassie F.,Parzefall W,knasmullers.2000.Single cell gel electrophoresis assay:a new technique for human biomonitoring studies.Mutation Research,463(1):13~31
Kawashima B.,Band J.A..1995.Metabolism and Excretion of Nitrobenzene by Rats and Mice.Toxicol APPL pharmacol,67(2):206~214
Kimelman D..2006.Mesodorm induction:from caps to chips.Nat Rev Genet,7(5):360~372.
Kimmel C.B.,Warga R.M..1988.Cell lineage and development potential of cell in the zebrafish embryo,Trends in Geneties,4(3):68~73
Klaude M.,Eriksson S.,Nygren J.,Ahnstrom G..1996.The comet assay: mechanisms and technical considerations,Mutation Researeh,363(2),89~96.
Krovel A.V.,Olsen L.C..2002.Expression of a vas EGFP transgene inprimordial germ cells of the zebrafish.Mech Dev,116(1~2):141~150
Krykhtin M.L. and E.I. Gorbach.1981.Reproductive ecology of the grass carp,Ctenopharyngodon idella, and the silver carp,Hypophthalmichthys molitrix,in the Amur Basin.Journal of Ichthyology,21(2):109~123
Laird C.A. and L.M..1996.Non-native fishes inhabiting the streams and lakes of Illinois.Illinois Natural History Survey Bulletin,35(1):1~51
Levin A.,Dent J.G..1982.Comparison of Metabolism of Nitrobenzene by Hepatic Microsomes and Cecal Microflora from Fisher-344 rats in Vitro and the Relative Importance of each in vivo.Drug Metab Dispos,10(5):450~454
Lewis K.E.,Eisen J.S..2003.From cells to circuits:development of the zebrafish spinal cord.Prog Neurobiol,69(6):419~449
Long Q.,Meng A.,Wang H.,et al.1997.GATA-1 expression pattern canbere capitulated in living transgenic zebrafish using GFP reporter gene.Development,124(20):4105~4111
Mahboob S. and A.N. Sheri.1997.Growth performance of major,common and some Chinese carps under composite culture system with special reference to pond fertilization.Journal of Aquaculture in the Tropics,12:201~207
McKenna D.J.,Rajab N.F.,McKeown S.R.,et al.2003.Use of the comet-FISH assay to demonstrate repair of the TP53 gene region in two human bladder carcinoma cell lines.Radiat Res,159(1):49~56
Malicki J.,Neuhauss S.C.,Schier A.F.,et al.1996.Mutations affecting development of the zebrafish retina.Development,123:263~273
McManus C..2005.Reversed bodies,reversedbrains, and (some) reversed behaviors:of zebrafish and men.DevCell,8 (6):796~797
McKelvey-Martin V.J.,Ho E.T.,McKeown S.R.,et al.1998.Emerging applications of the single cell gel electrophoresis (Comet) assay.I. Management of invasive transitional cell human bladder carcinoma. II. Fluorescent in situhybridization Comets for the identification of damaged and repaired DNA sequences in individual cells.Mutagenesis,13 (1):128 Meng A.,Jessen J.R.,Lin S.T..1999.ransgenesis.Methods Cell Biol,60:133~148 Montero J.A. ,Heisenberg C.P..2004.Gastrulation dynamics: cells Move into focus.Trends Cell Biol, 14 (11):620~627
Mulllins M.C.,Hammersehmidt M.,Haffter R.,et al..1994.Large-seale muta–genesisin the zebrafish in search of genese controlling development in a vertebrate.Curr Biol,4:189~202
Negonovskaya I.T. . 1980 . On the results and prospects of the introduction of phytophagous fishes into waters of the USSR.Journal of Ichthyology,20(4):101~111
Ng A.N.,de Jong-Curtain T.A.,Mawdsley D.J.,et al.2005.Formation of the digestive system in zebrafish:III.Intestinalepithelium morphogenesis.DevBiol,286(1):114~135.
Ober E.A.,Field H.A.,Stainier D.Y..2003.From endoderm formation to liver and pancreas development in zebrafish.MechDev,120(1):5~18
Olive P.L.,Wlodek D.,Banath J.P..1991.DNA double-strand breaks measured in individual cells subjected to gel electrophoresis.Cancer Researeh,51(17),4671~4676
?stling O.,Johanson K.J..1984.Microelectrophoretic study of radiation-induced DNA damages in individual mmamaliancells,Biochem Biophys Res Commun, 123(1):291~298
Parng C..2005.Invivo zebrafish assays for toxicity testing.Curr Opin Drug Discov Devel, 8(1):100~106
Pelegri F.2003.Maternal factors in zebrafish development.DevDyn,228(3):535~554
Rapp A.,Bock C.,Dittmar H.,et al.2000.UV-A breakage sensitivity of human chromosomes as measured by COMET-FISH depends on gene density and not on the chromosome size.J Photochem Photobiol B,56 (223):109~117
Raz E..2003.Primordial germ-cell development:the zebrafish perspective.Nat Rev Genet, 4(9):690~700
Rehenberg G.L..1987.DeveloPment Toxieity Evaluation of Inhaled Nitrobenzenein CD Rats.Fundam APPIT Oxieol,8(4):482~492
Rhinn M.,Picker A.,Brand M..2006.Global and local mechanisms of forebrain and midbrain patterning.Curr Opin Neurobiol,16(1):5~12
Ribetre F.,Amiard-Triquet C.,Boudou A.,et al.1995.Experimental study of interactions between five trace elements-Cu,Ag,Se,Zn,Hg,-toward their bioaccumulation by fish (Branchy danio rerio)from the direct route.Ecotoxicol Env Saf,32:1~11
Robinson D.,Smith J.N.,Williams R.T..1951.Studies in Detoxieation.40.The Metabolism of Nitrobenzene in the Rabbit:o-,m-and P-nitrophenols,o-,m-and P- aminophenolsand 4- nitrocatechol as Metabolites of Nitrobenzene.Bioehem J,50(2):228~235
Rydberg B.,Johanssen K.J..1978.Estimation of DNA strand breaks in single mmamalian cells,in Hnaawalt. PC,Friedberg EC and FoxCP(Eds.).DNA repair mechanisms,Academie press,NewYork,p465~468
Rydberg B..2000.Radiation induced heat-labile sites that convert into DNA double-strand brekas.Radiat Res,153(6) 805~812
Santos S.J.,Singh N.P.,Natarajan A.T..1997.Fluorescence in situ hybridization with comets.Exp Cell Res,232 (2):407~411
Schaeferhenrich A.,Sendt W.,Scheele J.,et al.2003 .Putative colon cancer risk factors damage global DNA and TP53 in primary human colon cells isolated from surgical samples. Food Chem Toxicol,41 (5):655~664
Schier A.F.,Talbot W.S..2005.Molecular genetics of axis formation in zebrafish.Annu Rev Genet,39:561~613
Schrank S.J.,and C.S. Guy.2002.Age,growth,and gonadal characteristics of adult bighead carp, Hypophthalmichthys nobilis, in the lower Missouri River.Environmental Biology ofFishes,64:443~450
Shedko S.V..2001.A list of cyclostomes and fishes of fresh waters along the coast of Primorsky. Pages 229~249 in Vladimir Ya. Levanidov’s Biennial Memorial Meetings 1, Dalnauka, Vladivostok,Russia,March 20~22
Silvina B. Nadin,Laura M. Vargas-Roig,Danial R. Ciocca.2001.A silver staining method for single-cell gel assay.Journal of Histochemistry & Cytochemistry,49(9):1183~1186
Singh W..1989.Fecundity of silver carp, Hypophthalmichthys molitrix (Val.).Indian Journal of Animal Sciences,59:392~394
Singh N.P..2000.Microgels for estimation of DNA strand breaks,DNA Protein crosslinks and apoptosis.Mutation Researeh,455(1-2):121~127
Singh N.P.,Mccoy M.T.,Tice R.R.,Sehneider E.L..1988.A single technique for quantification of low levels of DNA damage in individual cells.ExP.Cell Res,175(1):184~191
Soin S.G. and A.I. Sukhanova.1972.Comparative morphological analysis of the development of the grass carp , the black carp , the silver carp and the bighead (Cyprinidae).Journal of Ichthyology 12(1):61~71
Strehlow D. and Gilbert W. . 1993 . A fate map for the first eleavages of the zebrafish.Narure,201:451~453
Sun Z.,Amsterdam A.,Pazour G.J.,et al.2004.A genetic screenin zebrafish identifies ciliagenes as a principal cause of cystic kidney.Development,131(16):4085~4093
Thisse C.,Zon L.I..2002.Organogenesis-heart and blood formation from the zebrafish point of view.Science,295(5554):457~462
Tice R.R.,Agurell E.,Anderson D. et al.2000.Single cell gel comet assay:guide lines for in vitro and invivo genetic toxicology testing.Environ Mol Mutagen,35(3),206~221
Ungvary G.,Tatrai E.,Hudak A.,et al.1980.Studies on the embryotoxic effects of ortho- ,meta- ,and para-xylene.Toxicology,18(1):61~67
U.S. EPA. U.S. Environmental Protection Agency.1985.Health and Environmental Effects Profile for Nitrobenzene. Office of Solid Waste and Emergency Response,Washington,D.C., ECAO-CIN-P145.
Verigin B.V.,Shakha D.N. and B.G. Kamilov.1990.Correlation among reproductive indicators of the silver carp,Hypophthalmichthys molitrix,and the bighead,Aristichthys nobilis.Journal of Ichthyology ,30(8):80~92.
Verigin B.V.,A.P. Makeyeva and M.I. Zaki Mokhamed.1978.Natural spawning of the silver carp (Hypophthalmichthys nobilis).the bighead carp (Aristichthys nobilis).and the grass carp (Ctenopharyngodon idella) in the Syr-Dar’ya River.Journal of Ichthyology 18(1):143~146
Vinogradov V.K.,L.V. Erokhina,et al. 1966.Methods of artificial breeding of herbivorous fishes.Biological Abstracts 48(20),Abstract 99805, 1967
Vijayalaxm et al.1992.Assessment of radiation-induced DNA damage in human blood lymphocytes using the single-cell gel electrophoresis technique.Mutat Res,271 (3):43~52
Vitozzi L. & De Angelis G.A..1991.Critical review of comparative acute toxicity data on freshwater fish.Aquat Toxicol,19:167~204
Wang H.,Long Q.,Marty S.D.,et al.1998.A zebrafish model for hepatoery thropoie ticporphyria.Nat Genet,20(3):239~243
Weinstein B.M.,Stemple D.L.,Driever W.,et al.1995.Gridlock,a localized heritablevascular patterning defect in the zebrafish.Nat Med,1(11):1143~1147
Westerfield M..1993.The zebrafish book:a guide for the laboratory use of zebrafish Danio(Braehy danio)rerio.University of Oregon Press,pp-53
Whitfield T.T..2002.Zebrafish as a model for hearing and deafness.Neurobiol,53(2):157~171
Wilson S.W.,Houart C..2004.Early steps in the development of the forebrain.Dev Cell, 6(2):167~181
Xiao T.,Roeser T.,Staub W.,et al.2005.A GFP-based genetic Screen reveals mutations that disrupt the architecture of the zebrafish retinotectal projection.Development,132(13):2955~2967
Xie, P..2001.Gut contents of bighead carp (Aristichthys nobilis) and the processing and digestion of algal cells in the alimentary canal.Aquaculture,195:149~161
Zhu X.,Lin C.R.,Prefontaine G.G.,et al.2005.Genetic control of Pituitary development and hypopituitarism.Curr Opin Genet Dev,15(3):332~340
Zon L. I., Peterson R.T..2005.In vivo drug discovery in the zebrafish.Nat Rev Drug Discov,4(1):35~44