微囊藻毒素污染及其促肝癌作用研究进展

淡水水体的富营养化导致了蓝藻水华的普遍发生,微囊藻毒素是由蓝藻的部分藻属产生的环肽化合物,具有毒性大、分布广、结构稳定等特性,从而成为水环境中的重要潜在危害物质。微囊藻毒素已被证明具有明显的肝毒性,是肝肿瘤的促进剂之一。本文就微囊藻毒素的污染现状、肝毒性作用及其促肝癌机制等方面的研究进展进行了综述。     

藻毒素致癌性研究进展

从3个方面综述了藻毒素致癌性的研究进展，水体藻毒素污染业已成为一个世界性的环境问题，而藻毒素潜在的促癌作用更是引起了各界的广泛关注。结构效应关系研究，体外短期筛选实验以及动物诱癌试验结果均表明藻毒素具有促癌作用，提示抑制蛋白磷酸酶活性，诱导增殖相关基因异常表达以及细胞信号传导和分裂增殖失控是藻毒素可能的致癌机制。     

藻毒素的特性与其净水工艺选择

综述了藻毒素的基本特性，对几种净水工艺去除藻毒素的性能进行了比较和讨论。认为强化预处理＋常规工艺，常规工艺＋活性炭吸附，常规工艺＋膜技术处理是有效的净水工艺措施。     

二氧化钛光降解饮用水中藻毒素的研究进展

近年来随着含有大量氮、磷等营养物质的工业废水、生活污水及农田排水进入水体，藻类获取了丰富的营养物而大量繁殖。在世界范围内，包括很多作为饮用水水源的水库、湖泊在内的水体有大量蓝藻水华(Water bloom)形成。水华的爆发，不仅造成水体的感官性状恶化，而且由于某些藻类能分泌藻毒索，对人类健康构成危害。二氧化钛(TiO2)是一种优良的光催化剂，在废水处理、空气净化、抗菌等领域得到广泛应用。本文主要论述TiO2在降解饮用水中藻毒索方面的研究进展。     

微囊藻毒素致肝癌研究进展

流行病学研究及动物实验显示微囊藻毒素对人体健康具有损害效应。微囊藻毒素对肝脏的损害及作用机制是藻毒素生物学效应研究的重要内容，特别是微囊藻毒素在肝癌发生中的作用。本文综述了近年来国内外微囊藻毒素致肝癌的流行病学及实验研究、致癌作用机制，包括碱基损伤、染色体数目异常、DNA修复能力降低、调控细胞增殖和凋亡相关基因表达、抑制免疫系统等。     

藻毒素免疫抗原的制备及鉴定

目的为建立藻毒素(MCLR)免疫学检测方法,制备具免疫功能的MCLR完全抗原。方法根据MCLR分子中的羧基和蛋白质分子中的氨基,利用“活泼酯法”和“碳二亚胺法”分别制备MCLRKLH(匙孔血蓝蛋白)免疫抗原和MCLRBSA(牛血清白蛋白)检测抗原。结果用紫外光谱法(UV)和Bradford蛋白含量测定法鉴定,结合物中MCLR与KLH、BSA的结合摩尔比为9.1∶1和9.4∶1。采用“皮下注射法”用MCLRKLH免疫新西兰大白兔15周,取血清,用“间接酶联免疫吸附法”(id-ELISA)鉴定抗MCLR多克隆抗体效价,最高达1∶25600。结论证明制备的MCLRKLH具有免疫性。     

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

[目的]探讨饮水摄入微囊藻毒素在大鼠实验性肝癌形成模型中对遗传物质的损伤作用。[方法]建立微囊藻毒素促大鼠肝癌前病变的短期实验模型，检测饮水摄入低剂量微囊藻毒素在促肝癌作用的同时诱导骨髓嗜多染红细胞微核的作用。[结果]染毒组大鼹 骨髓嗜多染红细胞微核率明显升高。分别为：饮藻水 二乙基亚硝胺（DEN）启动组11.67‰，腹腔内注射微囊藻纯毒素 DEN启动组14.57‰，与DEN启动组6.80‰比较，有显著性差异。[结论]饮用受微囊藻毒素污染的水，可增强DEN对遗传物质的损伤。     

藻毒素对fos、jun基因表达及细胞周期的影响

目的 研究藻毒素对c-fos、c-jun表达及细胞周期的影响,探讨其可能的致癌机制。方法 将经色谱柱纯化的微囊藻毒素样品加入到SHE细胞培养体系中,用免疫组化方法分别于第1、3、6h观察细胞c-fos和c-jun蛋白表达,并用流式细胞仪分别检测细胞在第6、12、24h不同时相的周期改变情况。结果 微囊藻毒素可以诱导c-fos和c-jun持续高表达,6h后增高至5－6倍,具有明显的剂量反应关系;同时,藻毒素尚能介导G0／G1期细胞进入分裂状态,S、G2／M期细胞比例明显增加,24h后有44.9%细胞进入S期。结论 诱志细胞c-jun和c-fos异常表达并引起细胞过度增殖是微囊藻毒素可能的促癌机制之一。     

免疫方法在藻毒素及贝毒素检测中的应用

有害藻类自身或通过食物链在鱼类、贝类等生物体内蓄积,对生物直至人类产生危害。藻类毒素和贝毒的检测方法要求快速、方便、准确,并且在其含量极微时即可检出以起到预警作用。免疫方法使之成为可能。本文介绍了免疫测试技术的基本原理及其在藻毒素和贝毒检测中的应用,总结了该方法的应用前景和不足之处,旨在常规检测中推广和普及免疫方法。     

ELISA法与HPLC法检测太湖水中藻毒素的比较研究

目的：比较ELISA法与HPLC法检测水中微囊藻毒素含量的异同。方法：利用基于抗MC—LR多克隆抗体建立的间接竞争ELISA和HPLC法分别检测太湖中不同检测点、不同时期采集的大量水样中的MC—LR含量。结果：ELISA法和HPLC法相对误差平均值为8．62％，相关性检验t值为0．9996。在加标浓度为0．5～12．5ppb时，ELISA法回收率为94．84％～116．51％，HPLC法回收率为86．14％～92．18％。结论：两种方法具有良好的相关性，但ELISA法比HPLC法前处理简单，快速，回收率较好，更适合基层检测部门使用。     

微囊藻毒素诱导细胞凋亡和促进肿瘤发生的双重作用研究进展

微囊藻毒素（Microcystin）是世界各地水华中存在最普遍、危害最严重的一类藻类毒素,对环境和人类健康具有极大的危害性。以往研究表明,微囊藻毒素作为一种特异性的肝脏毒素,对细胞内蛋白磷酸酶具有强烈的抑制作用,表现为诱导细胞凋亡和促进肿瘤发生的双重毒性效应。本文简要综述报道微囊藻毒素诱导细胞凋亡和促进肿瘤生成双重毒性作用的研究进展。     

微囊藻毒素对人体健康影响的研究

目的 :研究微囊藻毒素对人体肝脏的损伤作用。方法 :采集不同程度污染微囊藻毒素的饮用水 ,以横断面调查方法 ,比较不同暴露组人群肝脏酶学指标的变化。结果 :3组不同暴露人群的 SGPT和 γ- GT的水平不同 ,其间存在统计学差异 (P<0 .0 5 )。　结论 :长期饮用受微囊藻毒素污染的沟、塘、河水可能造成肝脏功能损害     

高效液相色谱-串联质谱联用法测定饮用水中5种微囊藻毒素

目的建立液相色谱-串联质谱法同时测定饮用水中5种微囊藻毒素(MC-LR、MC-LW、MC-RR、MC-LF、MC-YR)检测的方法。方法采用直接进样方式,用高效液相色谱-串联质谱(HPLC/MS/MS)测定饮用水和水源水中的微囊藻毒素。水样经0.22μm微孔滤膜过滤,采用HPLC/MS/MS电喷雾电离阳离子(ESI+),多反应监测(MRM)模式检测,外标法定量。结果方法的线性范围为0.5～50.0μg/L,线性相关系数0.9994～1.0000,检出限0.06～0.08μg/L;高低两个水平的平均加标回收率分别为91.2%～102%和93.0%～99.0%;相对标准偏差(RSD)2.11%～3.264%;日内重复取样测定的RSD≤3.26%,日间重复取样测定的RSD≤4.36%。结论该方法可用于测定水中5种微囊藻毒素,方法操作简单、干扰少、快速、准确可靠,检测方法的检出限、精密度和加标回收率符合国家生活饮用水标准检验方法对质量控制的要求。     

太湖微囊藻毒素对细胞染色体及DNA损伤效应

目的研究太湖蓝藻水华中提取的微囊藻毒素的遗传毒性，探讨其对人类健康的潜在危害。方法应用小鼠骨髓嗜多染红细胞微核试验和单细胞凝胶电泳技术观察太湖蓝藻水华中微囊藻毒素引起的细胞染色体及DNA损伤效应。结果太湖蓝藻水华中提取的微囊藻毒素可明显增强小鼠骨髓嗜多染红细胞的微核率，并呈一定的剂量-反应关系；单细胞凝胶电泳技术显示可诱导中国仓鼠(V79)细胞DNA单链断裂，DNA断裂分级及细胞损伤率明显高于对照组。结论太湖蓝藻水华中提取的微囊藻毒素具有明显的遗传毒性，对人类健康存在潜在的远期危害。     

Effect of cacao liquor extract on tumor marker enzymes during chemical hepatocarcinogenesis in rats

This study investigated the effect of cacao liquor extract (CLE) on tumor marker enzymes--alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), glutathione-S-transferase (GST), and glutathione reductase (GR) activities--in plasma and/or liver of hepatocarcinogenic rats, which were induced with diethylnitrosamine and 2-acetylaminofluorene. Twenty-nine male Sprague-Dawley rats (weighing 150-330 g) were divided into four groups (n = 6-8): normal control group (N), normal group + CLE (NE), cancer group (C), and cancer group + CLE (CE). Analysis of variance showed significant differences (P<.05) in the specific activities of ALP, GGT, and GST between the C and N groups. However, GR activity for the C group was not significantly different compared with the N group. In the CE group, the specific activities of ALP, GGT, GST, and GR were significantly lower (P<.05) compared with the C group. The findings showed that CLE could lower the activity of tumor marker enzymes of rats during hepatocarcinogenesis. Based on the results obtained, polyphenol compounds present in the cacao liquor, extracted by using ethanol, have the potential in decreasing the severity of hepatocarcinogenesis.     

Effects of selenium supplementation on hepatocarcinogenesis in rats

Four groups of weanling male Wistar rats (Groups A—D) received diethylnitrosamine (DEN, 40 ppm) in their drinking water for four weeks; after a recovery period of two weeks, they received (for the rest of the experiment) phenobarbital (PB, 500 ppm) added to a Torula yeast‐based diet containing 0.17 ppm of selenium. Dietary selenium (2 ppm), as sodium selenite, was given to Group B one week before and during DEN treatment, to Group C one week before and during PB treatment, and to Group D during the entire experiment. Groups A and E received the unsupplemented diet, whereas Group E was not treated with DEN or PB. Pair‐feeding conditions were used to minimize possible influences of differences in food intake and growth. Rats were killed at the 19th and 24th weeks after the experiment began. No significant differences were found in food and fluid intakes or in growth rates among the groups. Livers in Group E were histologically normal, whereas preneoplastic and neoplastic lesions were found in all other groups. In rats killed at the 19th and 24th weeks, the numerical and the volumetric densities of preneoplastic lesions did not differ significantly between all the groups. Similarly, the incidence of hepatocellular carcinomas only detected at 24 weeks was not significantly different between the groups. These results indicated that in this particular model of hepatocarcinogenesis, the dietary supplementation of 2 ppm of selenium did not modify the development of preneoplasia and carcinomas.     

Effects of selenium supplementation on hepatocarcinogenesis in rats

Four groups of weanling male Wistar rats (Groups A-D) received diethylnitrosamine (DEN, 40 ppm) in their drinking water for four weeks; after a recovery period of two weeks, they received (for the rest of the experiment) phenobarbital (PB, 500 ppm) added to a Torula yeast-based diet containing 0.17 ppm of selenium. Dietary selenium (2 ppm), as sodium selenite, was given to Group B one week before and during DEN treatment, to Group C one week before and during PB treatment, and to Group D during the entire experiment. Groups A and E received the unsupplemented diet, whereas Group E was not treated with DEN or PB. Pair-feeding conditions were used to minimize possible influences of differences in food intake and growth. Rats were killed at the 19th and 24th weeks after the experiment began. No significant differences were found in food and fluid intakes or in growth rates among the groups. Livers in Group E were histologically normal, whereas preneoplastic and neoplastic lesions were found in all other groups. In rats killed at the 19th and 24th weeks, the numerical and the volumetric densities of preneoplastic lesions did not differ significantly between all the groups. Similarly, the incidence of hepatocellular carcinomas only detected at 24 weeks was not significantly different between the groups. These results indicated that in this particular model of hepatocarcinogenesis, the dietary supplementation of 2 ppm of selenium did not modify the development of preneoplasia and carcinomas.