饮用水源水中微囊藻毒素的遗传毒性与健康风险评价
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
随着水环境富营养化状况的日益加重,蓝藻水华在我国许多大型湖泊、水库中频频暴发,不仅造成水质恶化,水环境生态平衡失调,而且蓝藻所释放的毒素严重威胁着人民群众饮用水安全。自1878年动物饮用被蓝藻污染的水而引起死亡的事件首次报道以来,世界范围内已发生多起蓝藻毒素引起水生生物、鸟类及牲畜中毒或死亡的事件,其中最令人震惊的是1998年巴西Caruaru透析中心因误将藻毒素污染的水作为透析用水,结果造成116人中毒、52人死亡。
     微囊藻毒素(Microcystin,MC)是蓝藻水华中最常见、毒性最大的毒素之一。研究发现其中的MCLR亚型是一种强烈的肝脏肿瘤促进剂,IARC将其列为对人类可能致癌的化学物(Group 2B)。流行病学调查提示饮用水源中的MC与人群肝癌、大肠癌发病率以及男性胃癌死亡率上升具有相关性,MC、黄曲霉毒素和乙肝病毒已成为环境中致肝癌的三大危险因素。
     MC促肿瘤发生的作用机制至今尚未完全阐明。大量研究表明遗传物质改变可引发致畸、致癌、致突变等“三致效应”,“大多数致癌剂都是诱变剂”,发生在体细胞遗传物质的损害可能诱发肿瘤发生,生殖细胞的基因突变或染色体畸变是可遗传变异的来源,严重损害人类的基因库。近年来关于MC的遗传毒性和远期健康效应逐渐成为研究的热点,通过煮沸或常规饮用水处理工艺均不能完全消除水中MC,而饮用水安全与群众生活息息相关,研究饮用水源水中MC对人体娇档脑镀谛вΩ哂邢质狄庖濉?
     浙江省地处我国东南部沿海地区,水资源总量较为丰富,但由于人口密度高,人均水资源占有量低于全国平均水平。浙江省环境监测中心2007年对省内县级以上饮用水源地中176种有机污染物的调查结果显示,多处水源水受到不同程度的MC污染,以MCLR和MCRR两种亚型为主。尤其在太湖水系饮用水源地,由于太湖蓝藻频频爆发,水源水安全受到严重威胁。利用健康风险评价模型对水源水中有机污染物经饮水途径造成的健康风险研究在我省尚属首次,系统研究饮用水源水中微囊藻毒素可能具有的遗传毒性,探讨水源水中微囊藻毒素污染与人体健康的关系,对于饮用水源地环境保护和水质改善,城乡居民饮用水安全保障,具有十分重要的理论价值和现实意义。
     研究目的
     1.对浙江省县级以上饮用水源水检出有机污染物经饮水途径造成的健康风险度大小进行评价。
     2.针对水源水中的两种有机污染物MCLR和MCRR,运用短期遗传毒理学试验,对其可能导致的基因突变、DNA断裂和染色体损伤效应进行检测,探讨水源水中MCLR和MCRR对遗传物质的损伤作用。
     研究方法
     1.水源水中有机污染物的健康风险评价
     根据浙江省环境监测中心对101个县级以上饮用水源水中176种有机污染监测数据,利用US EPA推荐的水环境健康风险评价模型对水源水中检出的有机污染物经饮水途径所造成的致癌、非致癌健康风险进行评价。
     2.水源水中MC的遗传毒性研究
     采集MC污染较为严重的水源水样,将一部分水源水以固相萃取法提取浓集其中的MC,作为MC浓集物进行遗传毒性研究;另一部分水源水用作稀释MC纯品(MCLR和MCRR)的溶剂,模拟水源水中MC的不同污染程度,作为MC稀释水样进行遗传毒性研究;针对上述两部分样品,采用单细胞凝胶电泳试验检测了MC浓集物和MC稀释水样对人外周血淋巴细胞DNA可能的损伤;采用Ames试验检测了MC浓集物和MC稀释水样诱发基因突变的能力;采用鲤鱼外周血红细胞微核试验初步观察了MC浓集物和MC稀释水样对染色体畸变效应的影响。
     研究结果
     1.本次研究中,饮用水源水检出的主要有机污染物为草甘膦、MCLR、MCRR、DEHP、DBP和咔唑,MC(包括MCLR和MCRR)和草甘膦在水源水中分布较广,检出率较高。饮用水源水中有机污染引起的总体健康风险较小,但饮用水源仍存在一定的安全隐患。
     2.水源水中MC浓集物可诱导人淋巴细胞DNA链断裂损伤,MC稀释水样对DNA具有一定的损伤作用,水源水中除MC以外可能还存在其他的遗传毒物。
     3.Ames试验中MC浓集物和MC稀释水样均未观察到明显基因突变作用,但回变率随着剂量增加存在逐渐上升趋势。
     4.微核试验中未观察到MC浓集物对染色体的明显损伤,MC稀释水样一定程度上可诱发鲤鱼红细胞微核率上升,具有诱导染色体畸变的效应。
     结论
     1.水源水中检出的有机污染物浓度均较低,经饮水途径造成的健康风险度较小,远低于ICRP推荐的最大可接受水平。
     2.水源水中MC浓集物、水源水稀释MC在一定剂量下可诱导人淋巴细胞DNA损伤,锦鲤红细胞微核率上升,存在诱发DNA断裂和染色体损伤的效应,Ames试验中未见明显致突变性。
Eutrophocation has become the most important problem of water environment. Cyanobacterial blooms in lakes and reservoirs are known to occur throughout the world. These blue green alge blooms not only result in water quality deterioration, but also releases some toxins which bring severe threats to drinking water safety. Since first reported that wild animals died of drinking cyanobacterial contaminated water in 1878, lots of aquatic organism, birds and domestic animals were affected by microcystin. The most shocking human accident occurred at Caruaru hemodialysis center in Brazil in 1996, when 52 renal dialyzed patients died from liver failure resulting from cyanobacterial contamination of the water used for renal dialysis.
     Microcysin (MC) is one of the most common and potent cyanobacterial toxins. Research has indicated that microcystin which was evaluated as being Group 2B has tumor-promoting activity. Epidemiological studies have suggested that microcystin is a risk factor for the high incidence of primary liver cancer and high mortality of male stomach cancer in certain area where people have consumed water contaminated blue-green algae. It is reported that microcystin, hepatitis B virus and aflatoxin have become three main risk factors for liver cancer in environment.
     The tumor-promoting mechanism of microcystin is still not clear. It is known that the change of genetic materials in cells could induce carcinogenesis, teratogenesis and mutagenesis. Most cancer occurs because of genetic material change. It is well known that tumor development has close relationship with the damage of genetic materials.
     Zhejiang Province is situated on China's southeastern coast, on the southern part of the Yangzi River Delta. In this province, the total amount of water resources are relatively rich, but the average water resource per capita is below the mean level of the country because of the high population density. Based on the analysis data of organic pollutant in drinking water sources provided by Zhejiang Province Environment Monitoring Center, microcystin has become the main typical pollutant in drinking water sources, especially in Taihu Lake. It is the first health risk assessment of organic pollutants in drinking water sources in Zhejiang province. The genotoxicity study of microcystins in drinking water sources has profound theoretical and practical significance.
     Objective
     1. To evaluate the health risk caused by organic pollutants in drinking water sources via drinking water.
     2. To discuss the genotoxicity of MCLR and MCRR in drinking water source, measure DNA breakages by single cell gel electrophoresis (SCGE), investigate the mutagenicity by Ames test, and detect the chromosome damage by micronucleus test.
     Methods
     1. Health risk assessment of organic pollutants in drinking water source
     Based on the analysis data of organic pollutant in drinking water sources provided by Zhejiang province, a professional assessment model of water pollution was applied to evaluate the health risk caused by organic pollutants detected in drinking water sources.
     2. The genotoxicity of MC extracts and MC-containing water samples
     Surface water of 2 typical drinking water source A and B were sampled, which were relatively seriously polluted by MC. The diluted microcystins of MCLR and MCRR were added to the water samples respectively, while MC-containing purified water was prepared. The HLB resin was used to absorb and concentrate the microcystin in source water samples. The bacteria, human peripheral blood lymphocytes and ornamental carp erythrocyte were treated by purified water, drinking water source A and B, concentrated water samples, and MC-containing purified water, respectively. The mutation of bacterial DNA was assessed by Ames test. The DNA damage of human peripheral blood lymphocytes was tested by comet assay. Micronucleus of ornamental carp erythrocyte was measured by micronucleus test.
     Results
     1. Glyphosate, MCLR, MCRR, DEHP, DBP and carbazole are the main organic pollutants, and Glyphosate, MCLR, MCRR are typical organic pollutants in drinking water source in this study. The health risks caused by organic pollutant is relatively slight, the drinking source water is relatively safe.
     2. MC extracts and MC-containing purified water could result in DNA damage of human peripheral blood lymphocytes. Compared with pure MC, the level of DNA damage caused by MC-containing purified water has significant differences.
     3. Ames test showed that DNA mutation induced by MC extracts, pure MC and MC-containing purified water were not observed.
     4. MC-containing water samples were able to induce higher frequency of micronucleus in carp erythrocyte, while the chromosome damage induced by MC extracts were not observed.
     Conclusions
     1. The organic pollution degree in drinking water sources was relatively slightly, the health risk caused by organic pollutants in drinking water source was much lower than the maximum allowance levels recommended by ICRP.
     2. MC extracts and MC-containing water samples were able to induce DNA damage of human peripheral blood lymphocytes, increase frequency of micronucleus in carp erythrocyte, but DNA mutation in Ames test were not observed.
引文
[1]FRANDIS G.Poisonous Australian lake[J].Nature,1878,18(444):11-12.
    [2]ZIMBA P V,KHOO L,GAUNT P S,et al.Confirmation of catfish,Ictalurus punctatus(Rafinesque),mortality from Microcystis toxins[J].Journal of Fish Diseases,2001,24(1):41-47.
    [3]FALCONER I R.Toxic cyanobacterial bloom problems in Australian waters:risks and impacts on human health[J].Phycologia,2001,40(3):228-233.
    [4]JOCHIMSEN M,CARMICHAEL W,AN S,et al.Liver Failure and death after exposure to microcystins at a hemodialysis center in Brazil[J].New England Journal of Medicine,1998,338(2):873-878.
    [5]周伦,鱼达,余海,等.饮用水源中的微囊藻毒素与大肠癌发病的关系[J].中华预防医学杂志,2000,34(4):224-226.
    [6]徐明,杨坚波,林玉娣,等.饮用水微囊藻毒素与消化道恶性肿瘤死亡率关系的流行病学研究[J].中国慢性病预防与控制,2003,11(3):112-113.
    [7]俞顺章,赵宁,资晓林,等.饮水中微囊藻毒素与我国原发性肝癌关系的研究[J].中华肿瘤杂志,2001,23(2):69-89.
    [8]INGRID C,JAMIE B.Toxic cyanobacteria in water.London and New York[M].E&FN Spon Publisher,1999,6-25.
    [9]DE FIGUEIREDO D R,AZEITEIRO U M,ESTEVES S M,et al.Microcystin-producing blooms-a serious global public health issue[J].Ecotoxicology Environmental Safety,2004,59(2):151-163.
    [10]CODD G A,MORRISON L F,METCALF J S.Cyanobacterial toxins:risk management for health protection[J].Toxicology and Applied Pharmacology,2004,203(3):264-272.
    [11]徐海滨,陈艳,李芳,等.螺旋藻类保健食品生产原料及产品中微囊藻毒素污染现状调查[J].卫生研究,2003,32(4):339-343.
    [12]杨坚波,陈艳,林玉娣,等.太湖水域及鱼类体内微囊藻毒素的调查[J].环 境与健康杂志,2007,24(1):32-33.
    [13]XIE L Q,XIE P,OZAWA K,et al.Dynamics of microcystin-LR and-RR in the phytoplanktivorous silver carp in a subchronic toxicity experiment[J].Environ Pollution,2004,127(3):431-439.
    [14]林玉娣,俞顺章,徐明,等.无锡太湖水域藻类毒素污染与人群健康关系研究[J].上海预防医学杂志,2003,15(9):435-437.
    [15]MOHAMEDA Z A,SHEHRI A.Microcystins in groundwater wells and their accumulation in vegetable plants irrigated with contaminated waters in Saudi Arabia[J].Journal of Hazardous Materials,2009,172(1):310-315.
    [16]黄漪平.太湖水环境及其污染控制[M].北京:科学出版社,2001:1-104..
    [17]XIAO F G,ZHAO X L,TANG J,et al.Determination of Microcystin-LR in Water from Lake Tai,China[J].Bulletin of Environmental Contamination and Toxicology,2009,82(2):230-233.
    [18]纪荣平,李先宁,吕锡武.太湖梅梁湾水源水中微囊藻毒素浓度的变化[J].环境监测管理与技术,2007,19(3):20-22.
    [19]刘伟.巢湖蓝藻重度发生时的水质特征分析[J].中国环境监测,2007,23(4):101-102.
    [20]隋海霞,徐海滨,严卫星,等.淀山湖及鄱阳湖水体中微囊藻毒素的污染[J].环境与健康杂志,2007,24(3):136-138.
    [21]潘晓洁,常锋毅,沈银武,等.滇池水体中微囊藻毒素含量变化与环境因子的相关性研究[J].湖泊科学,2006,18(6):572-578.
    [22]张志红,赵金明,蒋颂辉,等.淀山湖夏秋季微囊藻毒素-LR和类毒素-A分布状况及其影响因素[J].卫生研究,2003,32(4):316-319.
    [23]隋海霞,严卫星,徐海滨,等.武汉东湖微囊藻毒素污染及其在鱼体内的动态研究[J].卫生研究,2004,33(1):39-41.
    [24]许川,舒为群,曹佳,等.重庆市及三峡库区水体微囊藻毒素污染研究[J].中国公共卫生,2005,21(9):1050-1052.
    [25]张娟,梁前进,周云龙,等.官厅水库水体中微囊藻毒素及其与微囊藻细胞密度相关性研究[J]_安全与环境学报,2006,6(5):53-56.
    [26]杨希存,王素凤,霍长友,等.秦皇岛洋河水库微囊藻毒素污染状况初探[J].环境与健康杂志,2009,26(1):54-55.
    [27]傅晓钦,徐能斌,朱丽波,等.宁波市饮用水源地爆发蓝藻水华时微囊藻毒素的污染分析[J].中国环境监测,2008,24(6):80-84.
    [28]杨希存,张洪霞.微囊藻毒素毒作用机制研究进展[J].河北医药,2009,31(16):2126-2128.
    [29]穆丽娜,陈传炜,俞顺章,等.太湖水体微囊藻毒素含量调查及其处理方法研究[J].中国公共卫生,2000,16(9):803-804.
    [30]张占英,俞顺章,卫国荣,等.微囊藻毒素LR在动物体内整体水平及细胞水平的分布[J].卫生毒理学杂志,2002,16(1):5-7.
    [31]CHEN J,XIE P,GUO L,et al.Tissue distributions and seasonal dynamics of the hepatotoxic microcystins-LR and -RR in a freshwater snail(Bellamya aeruginosa)from a large shallow,eutrophic lake of the subtropical China[J].Environmental Pollution,2005,134(3):423-430.
    [32]FAWELL J K,MITCHELL R E,EVERETT D J,et al.The toxicity of cyanobacterial toxins in the mouse:Ⅰ Microcystin-LR[J].Human &Experimental Toxicology,1999,18(3):162-167.
    [33]HUMPAGE A,FALCONER I R.Microcystin-LR and liver tumor promotion:effects on cytokinesis,ploidy,and apoptosis in cultured hepatocytes[J].Environmental Toxicology,1999,14(1):61-75.
    [34]BEASLEY V R,LOVELL R A,HOLMES K R,et al.Microcystin-LR decreases hepatic and renal perfusion,and causes circulatory shock,severe hypoglycemia,and terminal hyperkalemia in intravascularly dosed swine[J].Journal of Toxicology and Environmental Health Part A,2000,61(4):281-303.
    [35]MILUTINOVIC A,ZIVIN M,ZORC-PLESKOVIC R,et al.Nephrotoxic effects of chronic administration of microcystins -LR and -YR[J].Toxicon,2003,42(3):281-288.
    [36]赵金明,蒋颂辉,朱惠刚.藻毒素对实验性大鼠肝癌的促进作用[J].中国公共卫生,2003,19(6):694-696.
    [37]陈刚,俞顺章,UENO Y,et al.微囊藻毒素-LR和黄曲霉毒素B1对肝脏促癌作用的实验研究[J].癌变·畸变·突变,1996,8(3):129-132.
    [38]FALCONER I R.Tomur promotion and liver injury caused by oral consumption of cyanobacterial[J].Environmental Toxicology and Water Quality,1991,6:177-184.
    [39]连民,刘颖,俞顺章,等.饮水中微囊藻毒素对人群健康影响的横断面研究[J].中华流行病学杂志,2000,21(6):437-440.
    [40]Ueno Y,Nagata S,Tsutsumi T,et al.Detection of microcystins,a blue-green algal hepatotoxin,in drinking water sampled in Haimen and Fusui,endemic areas of primary liver cancer in China,by highly sensitive immunoassay[J].Carcinog,1996,17(6):1317-1321.
    [41]DING X S,LI X Y,DUAN H Y,et al.Toxic effects of Microcystis cell extracts on the reproductive system of male mice[J].Toxicon,2006,48(8):973-979.
    [42]LI Y,SHENG J,SHA J H,et al.The toxic effects of microcystin-LR on the reproductive system of male rats in vivo and in vitro[J].Reproductive Toxicology,2008,26(3-4):239-245.
    [43]张占英,连民,刘颖,等.微囊藻毒素LR对胎鼠的致畸和损伤作用[J].中国医学杂志,2002,82(5):345-347.
    [44]卫国荣,张占英,连民,等.微囊藻毒素LR对SD孕鼠胎盘的损伤作用研究[J].中国公共卫生,2002,18(8):921-922.
    [45]LI X Y,LIANG J B,HUANG P P.Toxic effects of microcystis cell extracts containing microcystin-LR on the blood of mice[J].Acta Hydrobiologica Sinica,2008,32(6):812-817.
    [46]RYMUSZKA A,SIEROSLAWSKA A,BOWNIK A,et al.In vitro effects of pure microcystin-LR on the lymphocyte proliferation in rainbow trout(Oncorhynchus mykiss)[J].Fish & Shellfish Immunology,2007,22(3):289-292.
    [47]LANKOFF A,CARMICHAEL W,GRASMAN K,et al.The uptake kinetics and immunotoxic effects of microcystin-LR in human and chicken peripheral blood lymphocytes in vitro[J].Toxicology,2004,204(1):23-40.
    [48]孙露,沈萍萍,周莹,等.太湖水华微囊藻毒素对小鼠免疫功能的影响[J].中国药理学与毒理学杂志,2002,16(3):226-230.
    [49]陈华,孙昌盛,王章敬,等.饮水微囊藻毒素在实验性肝癌形成中对遗传物质的损伤作用[J].海峡预防医学杂志,2002,8(5):1-3.
    [50]Rao P V,BHATTACHARYA R.The cyanobacterial toxin microcystin-LR induces DNA damage in mouse liver in vivo[J].Toxicology,1996,114(1):29-36.
    [51]ZEGURA B,LAH T,FILIPI M.The role of reactive oxygen species in microcystin-LR -induced DNA damage[J].Toxicology,2004,200(15):59-68.
    [52]詹立,张立实,王莉,等.微囊藻毒素Microcystin-LR体外遗传毒性[J].癌变.畸变.突变,2005,17(3):171-174.
    [53]张占英,俞顺章,陈传炜.微囊藻毒素LR对DNA和自然杀伤细胞的损伤效应研究[J].中华预防医学杂志,2001,35(2):75-78.
    [54]DING W X,SHEN H M,ZHU H G,et al.Genotoxicity of microcystic cyanobacteria extract of a water source in China[J].Mutation Reserach,1999,442(2):69-77.
    [55]宋瑞霞,刘征涛,沈萍萍.太湖微囊藻毒素对细胞染色体及DNA损伤效应[J].中国公共卫生,2004,20(12):1446-1447.
    [56]董玲,段丽菊,张慧珍,等.微囊藻毒素-LR致小鼠肝、肾和睾丸细胞DNA-蛋白质交联的研究[J].卫生研究,2008,37(2):144-146.
    [57]GAUDIN J,HUET S,JARRY G,et al.In vivo DNA damage induced by the cyanotoxin microcystin-LR:Comparison of intra-peritoneal and oral administrations by use of the comet assay[J].Mutation Research,2008,652(1):65-71.
    [58]黄奕龙,王仰麟,谭启宇,等.城市饮用水源地水环境健康风险评价及风险管理[J].地学前缘,2006,13(3):162-167.
    [59]曾光明,卓利,钟政林,等.水环境健康风险模型及其应用[J].水电能源学,1997,15(4):28-32.
    [60]厉以强,孙立伟,曲甍甍,等.人血淋巴细胞彗星试验检测南京市水源水的遗传毒性[J].南京大学学报(自然科学),2005,4l(3):330-334.
    [61]胡二邦.环境风险评价实用技术和方法[M],北京:中国环境科学出版社,2000.1-56.
    [62]National Academy of Science.Risk Assessment in the Federal Government:Managing the Process.Washington,D.C:National Academy Press,1983,1-44.
    [63]李如忠,石勇,王玉锋.淮河蚌埠段水环境健康风险评价[J].水电能源科学,2008,26(2):37-40.
    [64]许川,舒为群,罗财红,等.三峡库区水环境多环芳烃和邻苯二甲酸酯类有机污染物健康风险评价[J].环境科学研究,2007,20(5):57-60.
    [65]孙树青,胡国华,王勇泽,等.湘江干流水环境健康风险评价[J].安全与环境学报,2006,6(2):12-15.
    [66]USEPA.EPA/540/186060 Superfund public health evaluation manual[S].Washington DC:USEPA,1986.
    [67]CHORUS I,BARTRAM J.Toxic Cyanobacteria in Water.A Guide to Public Health Consequences,Monitoring and Management.London:E and FN Spon,1999,416-417.
    [68]王永杰,贾东红.健康风险评价中的不确定性分析[J].环境工程,2003,21(6):66-69.
    [69]曾光明,钟政林,曾北危.环境风险评价中的不确定性问题[J].中国环境科学,1998,18(3):252-255.
    [70]WANG J,PANG X,GE F,et al.An ultra-performance liquid chromatography-tandem mass spectrometry method for determination of microcystins occurrence in surface water in Zhejiang Province,China[J].Toxicon,2007,49(8):1120-1128.
    [71]乔敏,王春霞,黄圣彪,等.太湖梅梁湾水体和沉积物中有机污染物的遗传毒性[J].中国环境科学,2006,26(2):224-227.
    [72]徐凤丹,周世伟,范美云,等.浓集饮水致突变物程序规范化的研究[J].中国公共卫生学报,1993,12(2):84-86.
    [73]刘强,姜思海,李进,等.单细胞凝胶电泳技术对离体和整体照射致细胞DNA断裂的一致性研究[J].中国辐射卫生,2006,15(2):734-738.
    [74]SINGH P,MCCOY T,TICE R,et al.A simple technique for quantification of low level of DNA damege in individual cells[J].Experimental Cell Research,1988,175(1):184-191.
    [75]ALBERTINI J.Developing sustainable studies on environmental health[J].Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis,2001,480-481(1):317-331.
    [76]蔡宏道.现代环境卫生学[M].北京:人民卫生出版社.1995.
    [77]OSTELING O,JOHANSON K J.Microelectrophoretic study of radiation-induceed DNA damages in individual mammalian cells[J].Biochem Biophys Res Commun,1984,123:291-298.
    [78]RAJAGURU P,VIDYA L,BASKARASETHUPATHI B,et al.Genotoxicity evaluation of polluted ground water in human peripheral blood lymphocytes using the comet assay[J].Mutation Research,2002,517(1-2):29-37.
    [79]WHO.Cyanobacteria toxins:Microcystin-LR.Guidelines for drinking-water quality[M].World Health Organizition,Geneva,1998:95-110.
    [80]RAO P V L,BHATTACHARYA R,PARIDA M M,et al.Freshwater cyanobacterium microcystis aeruginosa(UTEX 2385) induced DNA damage in vivo and in vitro[J].Environmental Toxicology and Pharmacology,1998,5:1-6.
    [81]陈家平,翁登坡,傅文字等.微囊藻毒素LR对大鼠淋巴细胞DNA的损伤效应[J].水生生物学报,2004,28(6):677-678.
    [82]GAUDIN J,HEGARAT L L,NESSLANY F,et al.In vivo genotoxic potential of microcystin-LR:A cyanobacterial toxin,investigated both by the unscheduled DNA synthesis(UDS) and the comet assays after intravenous administration[J].Environmental Toxicology DOI 10.1002/tox.
    [83]PALUS J,DZIUBALTOWSKA E,STANCZYK M,et al.Biomonitoring of cyanobacterial blooms in Polish water reservoir and the cytotoxicity and genotoxicity of selected cyanobacterial extracts[J].International Journal of Occupational Medicine and Environmental Health,2007,20(1):48-65.
    [84]DING W X,SHEN H M,ZHU H G,et al.Genotoxicity of microcystic cyanobacteria extract of a water source in China[J].Mutation Research,1999,442:69-77.
    [85]宋瑞霞,刘征涛,沈萍萍.太湖中微囊藻毒素的遗传毒性研究[J].环境科学研究,2003,16(2):51-53.
    [86]吴和岩,苏瑾,施玮.微囊藻毒素-LR的DNA损伤作用研究[J].卫生研究,2005,34(6):690-693.
    [87]ZEGURA B,LAH TT,FILIPIC M,et al.Alteration of intracellular GSH levels and its role in microcystin-LR-induced DNA damage in human hepatoma HepG2cells[J].Mutation Research,2006,611:25-33.
    [88]ZEGURA B,VOLCIC M,LAH T T,et al.Different sensitivities of human colon adenocarcinoma(CaCo-2),astrocytoma(IPDDC-A2) and lymphoblastoid(NCNC)cell lines to microcystin-LR induced reactive oxygen species and DNA damage [J].Toxicon,2008,52:518-525.
    [89]MANKIEWICZ J,WALTER Z,TARCZYNSKA M,et al.Genototxicty of cyanobacterial extracts containing microcystins from Polish water reservoirs as determined by SOS chromotest and comet assay[J].Environmental toxicology,2002,17(4):341-350.
    [90]LANKOFF A,KRZOWSKI L,GLAB J,et al.DNA damage and repair in human peripheral blood lymphocytes following treatment with microcystin-LR[J].Mutation Research,2004,559:131-142.
    [91]金波,陈光荣.遗传毒理与环境检测[M].武汉:华中师范大学出版社,1998,145-158.
    [92]WU J Y,XU Q J,GAO G,et al.Evaluating genotoxicity associated with microcystin-LR and its risk to source water safety in Meiliang bay,Taihu lake[J].Environmental Toxicology,2006,21(3):250-255.
    [93]TSUJI K,WATANUKI T,KONDO F,et al.Stability of microcystins from cyanobacteria.-Ⅳ.Effect of chlorination on decomposition[J].Toxicon,1997,35(7):1033-1041.
    [94]王维,赵影,黄晓沐等.巢湖水有机污染物的遗传毒性及对饮用水水质的影响[J].癌变.畸变.突变,2004,16(6):352-354.
    [95]沈光平,王钦南,周社祯.微核与染色体畸变的相关性[J].遗传,1985,7(1):15-17.
    [96]AYLLON F,GARCIA-VAZQUEZ E.Micronuclei and other nuclear lesions as genotoxicity indicators in rainbow trout Oncorhynchus mykiss[J].Ecotoxicology and environmental safety,2001,49(3):221-225.
    [97]DE LEMOS T,RODEL M,TERRA R.Evaluation of basal micronucleus frequency and hexavalent chromium effects in fish erythrocytes[J].Environmental Toxicology & Chemistry,2001,20(6):1320-1324.
    [98]楼允东,吴萍.亚硝基胍对泥鳅红细胞微核及核异常的诱发[J].中国环境科学,1996,16(4):275-278.
    [99]李谷,程晓莉,陈丹,等.鱼微核试验筛检水体诱变物的应用与研究[J].水生生物学报,2002,26(1):74-82.
    [100]余文斌,李谷,王学会.镉对几种淡水鱼类外周血红细胞微核率的影响[J].湖北农学院学报,2000,20(4):354-357.
    [101]刘爱华,施立明.鱼类血细胞的微核测定[J].动物学研究,1985,1:8-10.
    [102]肖奇友,张尤恩,邱洪斌,等.鱼外周血红细胞微核率与采血时间、染毒次数关系的实验研究[J].癌变.畸变.突变,1992,4(1):40-41.
    [103]ZHAN L,SAKAMOTO H,SAKURABA M.Genotoxicity of microcystin-LR in human lymphoblastoid TK6 cells[J].Mutation Res,2004,557(1):1-6.
    [104]许川,舒为群,邱志群,等.绿茶对微囊藻毒素LR诱导肝细胞凋亡、Bcl-2表达及骨髓嗜多染红细胞微核的影响[J].畸变.癌变.突变,2007,19(1):29-32.
    [105]厉以强,柏仇勇,胡冠九,等.生物标志物在水源地风险评价中的作用与展望[J].环境污染与防治,2004,26(4):307-308.
    [1]CARMICHAEL W W.Health effects of toxin-producing Cyanobacteria."the CyanoHABs"[J].Human and Ecological Risk Assessment,2001,7(5):1393-1407.
    [2]CODD G A,MORRISON L F,METCALF J S.Cyanobacterial toxins:risk management for health protection[J].Toxicology and Applied Pharmacology,2005,203:264-272.
    [3]POURIA S,ANDRADE A DE,BARBOSA J,et al.Fatal microcystin intoxication in haemodialysis unit in Caruaru,Brazil[J].Lancet,1998,352:21-26.
    [4]CHORUS I,BARTRAM J.Toxic Cyanobacteria in water:A guide to their public health consequence,monitoring and management[M].Taylor & Francis,1999.
    [5]印木泉.遗传毒理学[M].北京:科学出版社,2002.
    [6]BRITTAIN S,MOHAMED Z A,WANG J,et al.Isolation and characterization of microcystins from a fiver Nile strain of oscillatoria tenuis Agardh ex Gomont[J].Toxicon,2000,38:1759-1771.
    [7]HARADA K,IMANISHI S,KATO H,et al.Isolation of Adda from microcystin-LR by microbial degradation[J].Toxicon,2004,44:107-109.
    [8]WHO.Guidelines for drinking-water quality.Third edition.Volume 1Recommendations.Chemical fact sheets.Geneva:World Health Organization [DB/OL].http://www.who.int/water sanitation health/dwq/gdwq3rev/en.
    [9]Overall Evaluation of Carcinogenicity to Humans[DB/OL]. http://monographs.iarc.fr/ENG/Classification/crthgr02b.php.
    [10]ERIKSSON J E,TOIVOLA D,MCRILUOTO JAO,et al.Hepatocyte deformation induced by cyanobacterial toxins reflects inhibition of protein phosphatases[J].Biochemical and Biophysical Research Communications,1990,173(3):1347-1353.
    [11]陈华,孙昌盛,胡志坚,等.饮水微囊藻毒素在大鼠肝癌发生期间对细胞增殖与凋亡的影响[J].癌变.畸变.突变,2002,14(4):214-217.
    [12]陈刚,俞顺章,卫国荣,等.肝癌高发区不同饮用水类型中微囊藻毒素含量调查[J].中华预防医学杂志,1996,3(1):6-9.
    [13]周伦,鱼达,余海等.饮用水源中的微囊藻毒素与大肠癌发病的关系[J].中华预防医学杂志,2000,34(4):224-226.
    [14]俞顺章,赵宁,资晓林,等.饮水中微囊藻毒素与我国原发性肝癌关系的研究[J].中华肿瘤杂志,2001,23(2):96-99.
    [15]DING WX,SHEN HM,ZHU HG,et al.Genotoxicity of microcystic cyanobacteria extract of a water source in China[J].Mutation Research,1999,442:69-77.
    [16]宋瑞霞,刘征涛,沈萍萍.太湖中微囊藻毒素的遗传毒性研究[J].环境科学研究,2003,16(2):51-53.
    [17]WU JY,XU Q J,GAO G,et al.Evaluating genotoxicity associated with microcystin-LR and its risk to source water safety in Meiliang bay,Taihu lake[J].Environmental Toxicology,2006,21(3):250-255.
    [18]TSUJI K,WATANUKI T,KONDO F,et al.Stability of microcystins from cyanobacteria.-Ⅳ.Effect of chlorination on decomposition[J].Toxicon,1997,35(7):1033-1041.
    [19]RUIZ-RUBIO M,HERA C,PUEYO C.Comparison of a forward and a reverse mutation assay in Salmonella typhimurium measuring L-arabinose resistance and histidine prototrophy[J].The EMBO Journal,1984,3:1435-1440.
    [20]HONMA M,SOFUNI T.The mouse lymphoma assay(MLA) using the microwell method[J].New York:Marcel Dekker Inc,2001:141-161.
    [21]ZHAN L,SAKAMOTO H,SAKURABA M,et al.Genotoxicity of microcystin-LR in human lymphoblastoid TK6 cells[J].Mutation Research,2004,557:1-6.
    [22]REPAVICH W M,SONZOGNI W C,STANDRIDGE J H,et al.Cyanobacteria(blue-green algae) in Wisconsin waters acute and chronic toxicity[J].Water Research,1990,24(2):225-231.
    [23]LANKOFF A,KRZOWSKI L,GLAB J,et al.DNA damage and repair in human peripheral blood lymphocytes following treatment with microcystin-LR[J].Mutation Research,2004,559:131-142.
    [24]HEDDLE J A,CIMINO M C,HAYASHI M,et al.Micronuclei as an index of cytogenetic damage:past,present,and future[J].Environmental and Molecular Mutagenesis,1991,18(4):277-291.
    [25]王红兵,朱惠刚.我国若干湖泊中蓝藻毒素的遗传毒性研究[J].中国公共卫生,1995,14(6):339-341.
    [26]赵影,杨志平,王志强,等.巢湖水藻类毒性及对饮用水水质影响[J].环境与健康杂志,2003,20(4):219-222.
    [27]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,1988,175(1):184-191.
    [28]RAO P V L,BHATTACHARYA R,PARIDA M M,et al.Freshwater cyanobacterium microcystis aeruginosa(UTEX 2385) induced DNA damage in vivo and in vitro[J].Environmental Toxicology and Pharmacology,1998,5:1-6.
    [29]张占英,俞顺章,陈传炜.微囊藻毒素LR对DNA和自然杀伤细胞的损伤效应研究[J].中华预防医学杂志,2001,35(2):75-78.
    [30]陈家平,翁登坡,傅文宇,等.微囊藻毒素LR对大鼠淋巴细胞DNA的损伤效 应[J].水生生物学报,2004,28(6):677-678.
    [31]GAUDIN J,HEGARAT L L,NESSLANY F,et al.In vivo genotoxic potential of microcystin-LR:A cyanobacterial toxin,investigated both by the unscheduled DNA synthesis(UDS) and the comet assays after intravenous administration[J].Environmental Toxicology DOI 10.1002/tox.
    [32]PALUS J,DZIUBALTOWSKA E,STANCZYK M,et al.Biomonitoring of cyanobacterial blooms in Polish water reservoir and the cytotoxicity and genotoxicity of selected cyanobacterial extracts[J].International Journal of Occupational Medicine and Environmental Health,2007,20(1):48-65.
    [33]吴和岩,苏瑾,施玮.微囊藻毒素-LR的DNA损伤作用研究[J].卫生研究,2005,34(6):690-693.
    [34]ZEGURA B,LAH T T,FILIPIC M.The role of reactive oxygen species in microcystin-LR-induced DNA damage[J].Toxicology,2004,200:59-68.
    [35]ZEGURA B,LAH T T,FILIPIC M,et al.Alteration of intracellular GSH levels and its role in microcystin-LR -induced DNA damage in human hepatoma HepG2cells[J].Mutation Research,2006,611:25-33.
    [36]ZEGURA B,VOLCIC M,LAH T T,et al.Different sensitivities of human colon adenocarcinoma(CaCo-2),astrocytoma(IPDDC-A2) and lymphoblastoid(NCNC)cell lines to microcystin-LR induced reactive oxygen species and DNA damage[J].Toxicon,2008,52:518-525.
    [37]MANKIEWICZ J,WALTER Z,TARCZYNSKA M,et al.Genototxicty of cyanobacterial extracts containing microcystins from Polish water reservoirs as determined by SOS chromotest and comet assay[J].Environmental toxicology,2002,17(4):341-350.
    [38]REIFFERSCHEID G,HEIL J.Validation of the SOS/umu test using test results of 486 chemicals and comparison with the Ames test and carcinogenicity data[J].Mutation Research,1996,369(3-4):129-145.
    [39]WILLIAMSG M.Detection of chemical carcinogens by unscheduled DNA synthesis in rat liver primary cell cultures[J].Cancer Research,1977,37:1845-1851.
    [40]施玮,朱惠刚.微囊藻毒素、藻类浓集物和藻细胞裂解液致突变性比较[J].上海环境科学,2003,22(8):532-535.
    [41]ASSILAKAKI M V,PFLUGMACHER S.Oxidative stress response of Synechocystis sp.(PCC 6803) due to exposure to microcystin-LR and cell-free cyanobacterial crude extract containing microcystin-LR[J].Journal of Applied Phycology,2008,20:219-225.
    [42]LANKOFF A,BIALCZYK J,DZIGA D,et al.Inhibition of nucleotide excision repair(NER) by microcystin-LR in CHO-Kl cells[J].Toxicon,2006,48:957-965.
    [1]INGRID C,JAMIE B.Toxic cyanobacteria in water.London and New York.E&FN Spon Publisher.1999.
    [2]FRANDIS G.Poisonous Australian lake[J].Nature,1878,18(444):11-12.
    [3]ZIMBA P V,KHOO L,GAUNT P S,et al.Confirmation of catfish,Ictalurus punctams(Rafinesque),mortality from Microcystis toxins[J].Journal of Fish Diseases,2001,24(1):41-47.
    [5]JOCHIMSEN M,CARMICHAEL W,AN S,et al.Liver Failure and death after exposure to microcystins at a hemodialysis center in Brazil[J].New England Journal of Medicine,1998,338(2):873-878.
    [6]SIVONEN K,NIEMELA S I,LEPISTO L,et al.Toxic cyanobacterial(blue-green algae) in finish fresh and coastal waters[J].Hydrobiologia,1990,190:267-275.
    [7]DUY T N,LAMP K S,SHAW G R.Toxicology and risk assessment of fresh water cyanobacterial(Blue-green algae) toxins in water[J].Reviews of Environmental Contamination and Toxicology,2000,163:113-186.
    [8]TSUJI K,WATANUKI T,KONDO F,et al.Stability of microcystins from cyanobacteria—Ⅱ.Effect of UV light on decomposition and isomerization[J].Toxicon,1995,33(12):1619-1631.
    [9]谢平.水生动物体内的微囊藻毒素及其对人类健康的潜在威胁[M].北京:科学出版社,2006,
    [10]WHO.Guidelines for drinking-water quality.Third edition. Volume 1 Recommendations.Chemical fact sheets.Geneva:World Health Organization[DB/OL].http://www.who.int/water sanitation_health/dwq/gdwq3rev /en.
    [11]黄漪平.太湖水环境及其污染控制[M].北京:科学出版社,2001:1-104..
    [12]XIAO F G,ZHAO X L,TANG J,et al.Determination of Microcystin-LR in Water from Lake Tai,China[J].Bulletin of Environmental Contamination and Toxicology,2009,82(2):230-233.
    [13]纪荣平,李先宁,吕锡武.太湖梅梁湾水源水中微囊藻毒素浓度的变化[J].环境监测管理与技术,2007,19(3):20-22.
    [14]杨坚波,陈艳,林玉娣,等.太湖水域及鱼类体内微囊藻毒素的调查[J].环境与健康杂志,2007,24(1):32-33.
    [15]刘伟.巢湖蓝藻重度发生时的水质特征分析[J].中国环境监测,2007,23(4):101-102.
    [16]隋海霞,徐海滨,严卫星,等.淀山湖及鄱阳湖水体中微囊藻毒素的污染[J].环境与健康杂志,2007,24(3):136-138.
    [17]潘晓洁,常锋毅,沈银武,等.滇池水体中微囊藻毒素含量变化与环境因子的相关性研究[J].湖泊科学,2006,18(6):572-578.
    [18]张志红,赵金明,蒋颂辉,等.淀山湖夏秋季微囊藻毒素-LR和类毒素-A分布状况及其影响因素[J].卫生研究,2003,32(4):316-319.
    [19]隋海霞,严卫星,徐海滨,等.武汉东湖微囊藻毒素污染及其在鱼体内的动态研究[J].卫生研究,2004,33(1):39-41.
    [20]许川,舒为群,曹佳,等.重庆市及三峡库区水体微囊藻毒素污染研究[J].中国公共卫生,2005,21(9):1050-1052.
    [21]张娟,梁前进,周云龙,等.官厅水库水体中微囊藻毒素及其与微囊藻细胞密度相关性研究[J].安全与环境学报,2006,6(5):53-56.
    [22]杨希存,王素凤,霍长友,等.秦皇岛洋河水库微囊藻毒素污染状况初探[J].环境与健康杂志,2009,26(1):54-55.
    [23]傅晓钦,徐能斌,朱丽波,等.宁波市饮用水源地爆发蓝藻水华时微囊藻毒素的污染分析[J].中国环境监测,2008,24(6):80-84.
    [24]杨希存,张洪霞.微囊藻毒素毒作用机制研究进展[J].河北医药,2009,31(16):2126-2128.
    [25]穆丽娜,陈传炜,俞顺章,等.太湖水体微囊藻毒素含量调查及其处理方法研究[J].中国公共卫生,2000,16(9):803-804.
    [26]DE FIGUEIREDO D R,AZEITEIRO U M,ESTEVES S M,et al.Microcystin-producing blooms-a serious global public health issue[J].Ecotoxicology Environmental Safety,2004,59(2):151-163.
    [27]CODD G A,MORRISON L F,METCALF J S.Cyanobacterial toxins:risk management for health protection[J].Toxicology and Applied Pharmacology,2004,203(3):264-272.
    [28]徐海滨,陈艳,李芳,等.螺旋藻类保健食品生产原料及产品中微囊藻毒素污染现状调查[J].卫生研究,2003,32(4):339-343.
    [29]XIE L Q,XIE P,OZAWA K,et al.Dynamics of microcystin-LR and-RR in the phytoplanktivorous silver carp in a subchronic toxicity experiment[J].Environ Pollution,2004,127(3):431-439.
    [30]林玉娣,俞顺章,徐明,等.无锡太湖水域藻类毒素污染与人群健康关系研究[J].上海预防医学杂志,2003,15(9):435-437.
    [31]MOHAMEDA Z A,SHEHRI A.Microcystins in groundwater wells and their accumulation in vegetable plants irrigated with contaminated waters in Saudi Arabia[J].Journal of Hazardous Materials,2009,172(1):310-315.
    [32]MIURA G A,ROBINSON N A,LAWRENCE W B,et al.Hepatotoxicity of microcystin-LR in fed and fasted rats[J].Toxicon,1991,29(3):337-346.
    [33]张占英,俞顺章,卫国荣,等.微囊藻毒素LR在动物体内整体水平及细胞水平的分布[J].卫生毒理学杂志,2002,16(1):5-7.
    [34]CHEN J,XIE P,GUO L,et al.Tissue distributions and seasonal dynamics of the hepatotoxic microcystins-LR and-RR in a freshwater snail(Bellamya aeruginosa)from a large shallow,eutrophic lake of the subtropical China[J].Environmental Pollution,2005,134(3):423-430.
    [35]FAWELL JK,MITCHELL RE,EVERETT DJ,et al.The toxicity of cyanobacterial toxins in the mouse:Ⅰ Microcystin-LR[J].Human &Experimental Toxicology,1999,18(3):162-167.
    [36]HUMPAGE A,FALCONER IR.Microcystin-LR and liver tumor promotion:effects on cytokinesis,ploidy,and apoptosis in cultured hepatocytes[J].Environmental Toxicology,1999,14(1):61-75.
    [37]BEASLEY VR,LOVELL RA,HOLMES KR,et al.Microcystin-LR decreases hepatic and renal perfusion,and causes circulatory shock,severe hypoglycemia,and terminal hyperkalemia in intravascularly dosed swine[J].Journal of Toxicology and Environmental Health Part A,2000,61(4):281-303.
    [38]MILUTINOVIC A,ZIVIN M,ZORC-PLESKOVIC R,et al.Nephrotoxic effects of chronic administration of microcystins-LR and-YR[J].Toxicon,2003,42(3):281-288.
    [39]赵金明,蒋颂辉,朱惠刚.藻毒素对实验性大鼠肝癌的促进作用[J].中国公共卫生,2003,19(6):694-696.
    [40]陈刚,俞顺章,UENO Y,et al.微囊藻毒素-LR和黄曲霉毒素Bl对肝脏促癌作用的实验研究[J].癌变·畸变·突变,1996,8(3):129-132.
    [41]FALCONER IR.Tomur promotion and liver injury caused by oral consumption of cyanobacterial[J].Environmental Toxicology and Water Quality,1991,6:177-184.
    [42]连民,刘颖,俞顺章,等.饮水中微囊藻毒素对人群健康影响的横断面研究[J].中华流行病学杂志,2000,21(6):437-440.
    [43]Ueno Y,Nagata S,Tsutsumi T,et al.Detection of microcystins,a blue-green algal hepatotoxin,in drinking water sampled in Haimen and Fusui,endemic areas of primary liver cancer in China,by highly sensitive immunoassay[J].Carcinog,1996,17(6):1317-1321.
    [44]俞顺章,赵宁,资晓林,等.饮水中微囊藻毒素与我国原发性肝癌关系的研究[J].中华肿瘤杂志,2001,23(2):69-89.
    [45]周伦,鱼达,余海,等.饮用水源中的微囊藻毒素与大肠癌发病的关系[J].中华预防医学杂志,2000,34(4):224-226.
    [46]徐明,杨坚波,林玉娣,等.饮用水微囊藻毒素与消化道恶性肿瘤死亡率关系的流行病学研究[J].中国慢性病预防与控制,2003,11(3):112-113.
    [47]DING XS,LI XY,DUAN HY,et al.Toxic effects of Microcystis cell extracts on the reproductive system of male mice[J].Toxicon,2006,48(8):973-979.
    [48]LI Y,SHENG J,SHA JH,et al.The toxic effects of microcystin-LR on the reproductive system of male rats in vivo and in vitro[J].Reproductive Toxicology,2008,26(3-4):239-245.
    [49]张占英,连民,刘颖,等.微囊藻毒素LR对胎鼠的致畸和损伤作用[J].中国医学杂志,2002,82(5):345—347.
    [50]卫国荣,张占英,连民,等.微囊藻毒素LR对SD孕鼠胎盘的损伤作用研究[J].中国公共卫生,2002,18(8):921-922.
    [51]LI XY,LIANG JB,HUANG PP.Toxic effects of microcystis cell extracts containing microcystin-LR on the blood of mice[J].Acta Hydrobiologica Sinica,2008,32(6):812-817.
    [52]RYMUSZKA A,SIEROSLAWSKA A,BOWNIK A,et al.In vitro effects of pure microcystin-LR on the lymphocyte proliferation in rainbow trout(Oncorhynchus mykiss)[J].Fish & Shellfish Immunology,2007,22(3):289-292.
    [53]LANKOFF A,CARMICHAEL W,GRASMAN K,et al.The uptake kinetics and immunotoxic effects of microcystin-LR in human and chicken peripheral blood lymphocytes in vitro[J].Toxicology,2004,204(1):23-40.
    [54]孙露,沈萍萍,周莹,等.太湖水华微囊藻毒素对小鼠免疫功能的影响[J].中国药理学与毒理学杂志,2002,16(3):226-230.
    [55]MACKINTOSH C,BEATTIE K,KLUMPP S,et al.Cyanobacterial microcystin-LR is a potent and specific inhibitor of protein phosphatases 1 and 2A from both mammals and higher plants[J].FEBS,1990,264(2):187-192.
    [56]毛国根,徐立红,叶少菁.微囊藻毒素-LR致肝细胞连接通讯下调的研究[J].中国环境科学,2003,23(1):34-37.
    [57]MEREISH K A,SOLOW R,et al.Effect of antihepatotoxic agents against mcrocystin-LR toxicity in cultured rat hepatocytes[J].Pharm Res,1990,7:256-259.
    [58]MAIDAN M,CARLIS V,GALHARD F G,et al.Effects of microcystin over short-and long-term memory and oxidative stress generation in hippocampus of rats[J].Chemico-Biological Interactions,2006,159(3):223-224.
    [59]MORENOA I,PICHARDOA S,JOS A,et al.Antioxidant enzyme activity and lipid peroxidation in liver and kidney of rats exposed to microcystin-LR administered intraperitoneally[J].Toxicon,2005,45(4):295-402.
    [60]JAYARAJ R,ANAND T,LAKSHMANA RAO P V.Activity and gene expression profile of certain antioxidant enzymes ton microcystin-LR induced oxidative stress in CaCo2 cells[J].Toxicon,2004,43(1):85-92.
    [61]NICOLETTE B,MICHELLE MG,TIM GD,et al.The role of microcystin-LR in the induction of apoptosis and oxidative stress in CaCo2 cells[J].Toxicon,2004,43(1):85-92
    [62]吴和岩,苏瑾,施玮.微囊藻毒素.LR诱导肝细胞氧化应激[J].中国公共卫生,2006,22(2):184-185.
    [63]PRIETO A I,JOS A,PICHARDO S,et al.Differential oxidative stress responses to microcystins LR and RR in intraperitoneally exposed tilapia fish(Oreochromis sp.)[J].Aquatic Toxicology,2006,77(3):314-321.
    [64]PUERTO M,PICHARDO S,JOS A,et al.Differential oxidative stress responses to pure Microcystin-LR and Microcystin-containing and non-containing cyanobacterial crude extracts on Caco-2 cells[J].Toxicon,2009,doi:10.1016/j.toxicon.2009.10.003
    [65]Toivola D M,Eriksson J E.Toxins affecting cell signalling and alteration of cytoskeletal structure.Toxicology in Vitro,1999,13(45):521-530.
    [66]LI H,XIE P,LI G,et al.In vivo study on the effects of microcystin extracts on the expression profiles of proto-oncogenes(c-fos,c-jun and c-myc) in liver,kidney and testis of male Wistar rats injected i.v.with toxins[J].Toxicon,2009,53(1):169-175.
    [67]BOTHA N,GEHRINGER M M,DOWNING T G,et al.The role of microcystin-LR in the induction of apoptosis and oxidative stress in Caco-2 cells [J].Toxicon,2004,43:85-92.
    [68]FU WY,CHEN JP,WANG XM,et al.Altered expression of p53,Bcl-2 and Bax induced by microcystin-LR in vivo and in vitro[J].Toxicon,2005,46(2):171-177.
    [69]陈加平,徐立红,傅文字,等.微囊藻毒素LR诱导大鼠NRK细胞Bax蛋白表达[J].水生生物学报,2004,28(7):450-451.
    [70]胡志坚,陈华,李一伟,等.微囊藻毒素促肝癌过程中肝细胞bcl-2及Bax基因表达研究[J].中华预防医学杂志,2002,36(4):239-242.
    [71]胡志坚,陈华,李一伟,等.微囊藻毒素促肝癌过程中肝细胞PCNA、p21~(wafl)基因表达研究[J].中国公共卫生,2002,18(5):538-540.
    [72]傅文字,陈加平,徐立红.Caspase-3在微囊藻毒素诱导的细胞凋亡中的作用[J].中国环境科学,2004,24(1):6-8.
    [73]陈华,孙昌盛,王章敬,等.饮水微囊藻毒素在实验性肝癌形成中对遗传物质的损伤作用[J].海峡预防医学杂志,2002,8(5):1-3.
    [74]Rao PV,BHATTACHARYA R.The cyanobacterial toxin microcystin-LR induces DNA damage in mouse liver in vivo[J].Toxicology,1996,114(1):29-36.
    [75]ZEGURA B,LAH T,FILIPI M.The role of reactive oxygen species in microcystin-LR -induced DNA damage[J].Toxicology,2004,200(15):59-68.
    [76]詹立,张立实,王莉,等.微囊藻毒素Microcystin-LR体外遗传毒性[J].癌变.畸变.突变,2005,17(3):171-174.
    [77]张占英,俞顺章,陈传炜.微囊藻毒素LR对DNA和自然杀伤细胞的损伤效应研究[J].中华预防医学杂志,2001,35(2):75-78.
    [78]DING W X,SHEN H M,ZHU H G,et al.Genotoxicity of microcystic cyanobacteria extract of a water source in China[J].Mutation Reserach,1999,442(2):69-77.
    [79]宋瑞霞,刘征涛,沈萍萍.太湖微囊藻毒素对细胞染色体及DNA损伤效应[J].中国公共卫生,2004,20(12):1446-1447.
    [80]董玲,段丽菊,张慧珍,等.微囊藻毒素-LR致小鼠肝、肾和睾丸细胞DNA-蛋白质交联的研究[J].卫生研究,2008,37(2):144-146.
    [81]GAUDIN J,HUET S,JARRY G,et al.In vivo DNA damage induced by the cyanotoxin microcystin-LR:Comparison of intra-peritoneal and oral administrations by use of the comet assay[J].Mutation Research,2008,652(1):65-71.
    [82]WHO.Cyanobacteria toxins:Microcystin-LR.Guidelines for drinking-water quality[M].World Health Organizition,Geneva,1998:95-110.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700