大黄素和大黄酸的体外遗传毒性评价

目的：评价大黄素和大黄酸的体外遗传毒性。方法：使用不同浓度的大黄素和大黄酸（均分别为20、40、80、120μg/ml）处理人的类淋巴母细胞WTK1后,进行彗星实验、体外微核试验和TK基因突变试验。并设溶剂对照组和甲基甲烷磺酸（mthylmethane sulfonate,MMS）阳性对照组。结果：大黄素80和120μg/ml剂量组TK基因突变频率、细胞拖尾率及平均尾长均增高（P〈0.05）;大黄酸120μg/ml剂量组TK位点总突变频率增高（P〈0.05）。结论：在本实验条件下,大黄素和大黄酸均表现出弱致突变作用。     

适合纳米材料遗传毒性评价方法的选择

纳米材料独特的小尺寸和大的比表面积等物理化学性质,及其与生物体相互作用的高活性特性,为其在多种领域提供了广阔应用前景。与此同时,也可能带来潜在的安全风险。纳米材料的代谢和分布方式与普通化合物存在一定差异,如何科学地评价纳米材料对人体的潜在毒性风险,尤其是遗传毒性,是目前科学界及各相关监管部门亟需解决的问题。本文对现有常用遗传毒性评价方法用以评价纳米材料时存在的试验体系的局限性和灵敏度方面存在的优势与劣势进行回顾,总结了纳米材料遗传毒性评价时的关注点;并基于经济合作与发展（OECD）专家工作组的相关建议及相关遗传毒性评价指导原则,初步提出纳米材料遗传毒性试验组合优化方案。以期填补相关领域的空白,为纳米材料毒性评价和含纳米材料产品的上市前技术审评工作提供有益的借鉴。     

盐酸苯海拉明咖啡因复方的遗传毒性评价

目的：研究盐酸苯海拉明咖啡因复方(盐酸苯海拉明/咖啡因质量比为1/2.4)是否具有遗传毒性。方法：采用鼠伤寒沙门氏菌回复突变试验(Ames试验),体外培养中国仓鼠肺(CHL)细胞染色体畸变试验和ICR小鼠骨髓微核试验检测盐酸苯海拉明咖啡因复方的遗传毒性。Ames试验选用TA97、TA98、TA100、TA102及TA1535为指示菌株,设0.5、5、50、500、5 000 mg/皿共5个受试剂量组;CHL细胞染色体畸变试验设低、中、高(分别为8.45、16.9、33.8 mg/mL)3个剂量组;小鼠骨髓微核试验采用ICR小鼠经口灌胃的方式一次给予盐酸苯海拉明咖啡因复方,设低、中、高3个剂量组,分别为21.59、43.17和86.35 mg/kg。结果：与对照组相比,Ames试验结果提示在0.5、5、50、500、5 000 mg/皿剂量下,在加和不加代谢活化系统S9时对鼠伤寒沙门氏菌均无致突变性(P>0.05)。CHL细胞染色体畸变试验结果提示在终浓度8.45、16.9和33.8 mg/mL剂量组,在加与不加S9代谢活化系统培养CHL细胞24 h和4 h的条件下均未诱发染色体畸...     

龙葵果的急性毒性和遗传毒性试验

背景与目地：研究龙葵果的急性毒性和遗传毒性,为龙葵果汁作为保健食品进一步开发的利用打下基础。材料与方法：小鼠急性毒性试Ames试验、微核试验和精子畸形试验采用《保健食品安全性评价程序和检验方法规范》要求进行。结果：龙葵果汁急性分组属于无毒级别。Ames试验、微核试验和精子畸形试验结果均为阴性。结论：在本次实验条件下,未见小鼠口服急性毒性和遗传毒性作用。     

多溴联苯醚BDE-3、BDE-47和BDE-209的体外遗传毒性评价

目的：对3种代表性多溴联苯醚（PBDEs）BDE-3、BDE-47和BDE-209进行体外遗传毒性评价。方法：采用TK6人淋巴母细胞进行彗星试验、微核试验和TK基因突变试验,同时检测DNA损伤、染色体改变和基因突变3个遗传学终点。每种PBDEs均设定5个剂量组：BDE-3为60、90、120、180和240 μmol/L;BDE-47为60、120、180、200和240 μmol/L;BDE-209为24、40、120、180和240 μmol/L;同时设定溶媒DMSO为阴性对照组。结果：与阴性对照组比较,3种PBDEs在各个剂量下均未能引起TK6细胞彗星的尾长、尾部DNA百分数和尾矩的增加（P > 0.05）,也均未引起TK6细胞微核率升高（P > 0.05）。TK基因突变试验显示,3种PBDEs均能引起TK基因突变频率升高,差异具有统计学意义（P < 0.05）,并呈剂量依赖性升高趋势（相关系数[R_BDE-3²]=0.85,[R_BDE-47²]=0.85,[R_BDE-209²]=0.90;P < 0.05）,但致突变作用BDE-47强于BDE-3和BDE-209。结论：多溴联苯醚BDE-3、BDE-47和BDE-209对TK6细胞具有致突变作用。     

成核透明剂ZC-3的急性毒性和遗传毒性试验

背景与目的:研究成核透明剂ZC-3(DMDBS)的急性毒性和遗传毒性.材料与方法:小鼠急性毒性试验、Ames试验、小鼠骨髓嗜多染红细胞微核试验、小鼠精子畸形试验.结果:急性毒性试验表明:成核透明剂ZC-3属无毒物质.Ames试验、微核试验和精子畸形试验结果均为阴性.结论:在本次实验条件下,成核透明剂ZC-3为无毒物质,未显示有遗传毒性作用.     

溪黄草袋泡茶的急性毒性和遗传毒性研究

目的： 探讨溪黄草袋泡茶的急性毒性和遗传毒性。方法：急性毒性实验,分别对小鼠灌服剂量为21.5、10.0、4.64、2.15 g/kg的溪黄草袋泡茶提取液,采用霍恩氏(Horn)法计算其半数致死剂量(LD50)。设每皿5 000、1 000、200、40、8 μg共5个剂量组进行Ames试验;分别按 10.0、5.00、2.50 g/kg进行小鼠骨髓嗜多染红细胞微核试验和小鼠精子畸形试验,检测溪黄草袋泡茶的遗传毒性。结果：溪黄草袋泡茶对雌雄小鼠LD50＞21.5 g/kg;Ames试验中,溪黄草袋泡茶对 TA97、TA98、TA100、TA102这4种试验菌株,在加与不加S9条件下,样品各剂量组回变菌落数均未超过溶剂对照组菌落数的2倍,亦无剂量-反应关系;小鼠骨髓嗜多染红细胞微核试验和精子畸形试验结果显示,各剂量组的微核率和精子畸形率与阴性对照组比较差异均无统计学意义(P>0.05)。结论：在本实验条件下,溪黄草袋泡茶属无毒级物质,未见遗传毒性。     

保健食品Glucosol的遗传毒性试验研究

Glucosol是一种降血糖保健食品,出口台湾和东南亚各地。为了考察是否存在遗传毒性,按照台湾的有关规程进行了试验。Ames试验采用组氨酸营养缺陷型鼠伤寒沙门氏杆菌TA97、TA98、TA100、TA102和TA1535五个菌株,试验在有或无代谢活化剂下对受试物1－10000μg／皿共5个浓度进行计数。结果在10000μg/皿未见菌株出现毒性反应,10000μg／皿以下各浓度组不引起各菌株回变菌落数的明显增加。染色体畸变试验采用传供的中国仓鼠肺细胞（CHL）,试验在有或无代谢活化剂下,对受试物250－1000μg/ml3个浓度,两个培养时间（24和48h)进行显微镜下计数。结果50％细胞生长抑制浓度为1250μg/ml以下各浓度组的细胞畸变率均＜3％。微核试验采用NIH种小鼠,在2.5/-10.0g/kg3个剂量下连续2d灌胃给予受试物,30h取股骨骨髓制片,显微镜下计数。结果10.0g/kg以下各剂量组的骨髓嗜多染红细胞的微核率均＜4‰。精子畸形试验采用昆明种小鼠,在2.5g/kg-10.0g/kg3个剂量连续5d灌胃给予受试物,35d后取附睾尾精子制片,显微镜下计数。结果10.0g/kg以下各剂量组的精子畸形率均＜2．8％。4项致突变试验均为阴性结果。提示该受试物不存在体外基因突变和体内、外染色体畸变和雄性生殖细胞的遗传损伤。     

甘泰康的遗传毒性研究

目的与方法:采用Ames试验、小鼠骨髓嗜多染红细胞微核试验及小鼠精子畸形试验检测甘泰康的遗传毒性,为其食用安全性提供依据.结果与结论:3项遗传毒性试验均为阴性,甘泰康对所试菌株、小鼠体细胞及雄性生殖细胞无诱变性.     

乙二胺为核心的PAMAM树枝状聚合物(5.0代)纳米材料溶液的遗传毒性研究

目的:研究乙二胺为核心的PAMAM树枝状聚合物(5.0代)纳米材料溶液的遗传毒性。方法:采用Ames试验平板掺入法,设3 985、797、139.4、31.88和6.376 μg/皿的5个乙二胺为核心的PAMAM树枝状聚合物(5.0代)溶液浓度组,在加与不加S9混合液的条件下观察回变菌落数。同时采用L5178Y细胞胞质分裂阻滞微核细胞组学试验,给予受试细胞终浓度分别为0.625、1.25、2.5、5、10 μg/mL的受试物,观察其微核组效应、剂量-效应和时间-效应关系。结果:受试物溶液各剂量组均未引起测试菌株回变菌落数明显增加,Ames试验结果为阴性。胞质分裂阻滞微核细胞组学试验中,与阴性对照组比较,1.25 μg/mL的受试物即可诱导受试细胞出现核芽(P<0.01);2.5 μg/mL及以上剂量可进一步诱使细胞出现总微核、Ⅰ型微核、Ⅱ型微核和核质桥效应(P<0.01),且存在明显的剂量-效应关系(除核质桥外,r值均>0.5,P均<0.05)。与阴性对照组比较,在5 μg/mL剂量下,乙二胺为核心的PAMAM树枝状聚合物(5.0代)溶液在9 h时即可诱导受试细胞的总微核、Ⅰ型微核、Ⅱ型微核和核芽增加(P<0.01);在18 h时出现核质桥数增加(P<0.01),各项指标在27 h达到峰值。结论:乙二胺为核心的PAMAM树枝状聚合物(5.0代)溶液对鼠伤寒沙门氏菌无致基因突变作用;对L5178Y细胞可诱导4类微核组效应,并有明显的剂量-效应和时间-效应关系;从剂量和时间来看,以核芽效应最为敏感。     

甲基丙烯酸环氧丙酯的遗传毒性评价

目的：观察甲基丙烯酸环氧丙酯（GMA）诱发体外培养的中国仓鼠肺细胞（V79）微核发生变化情况,对其遗传毒性进行评价。方法：分别采用不同浓度（2.25、4.5、9.0、18.0、36.0 μg/mL）的GMA染毒V79细胞,设置空白对照组和DMSO溶剂对照组,其中染毒3 h处理组分别在加和不加体外活化系统（S9）条件下进行,染毒24 h处理组在不加S9条件下进行。分别计算细胞复制指数和微核细胞率。结果：GMA的浓度在2.25~36.0 μg/mL范围内,无S9的条件下,与空白对照组和DMSO溶剂对照组相比,GMA染毒3和24 h组的V79细胞复制指数均无明显变化,但微核细胞率明显升高,并呈浓度-效应关系;在有S9的条件下染毒3 h,各剂量组的GMA诱发微核细胞率的差异均无统计学意义。结论：在2.25~36.0 μg/mL浓度范围,GMA可致V79细胞的微核率升高,表明GMA可诱发遗传物质损伤,具有遗传毒性。     

Genotoxicity Testing and Biomarker Studies on Surface Waters: An Overview of the Techniques and Their Efficacies

Rapid industrialization, use of modern agriculture practices, and fast urbanization vis-a-vis indiscriminate use of xenobiotics have led to the serious problems of water pollution in India and abroad. The complexicity of the pollutants in environmental samples demands a multitude of genotoxicity testing with increasing simplicity, sensitivity, and affordability. Moreover, various pollutants mutually affect their own toxic behavior, which complicates the problem of risk assessment. An overview, highlighting the genotoxicity testing system, such as Ames plate incorporation test, Ames fluctuation test, E. coli survival assay, Allium cepa toxicity/genotoxicity test, comet assay, and plasmid nicking assay, is presented in this article, and a comparison has been made to estimate the efficacy of these genotoxicity bioassays performed on some surface waters. Some work on toxicity biomarkers vis-a-vis studies on surface waters has also been included in the present review.     

Unequivocal evidence of genotoxic potential of argemone oil in mice

Consumption of mustard oil adulterated with argemone oil leads to a clinical condition, commonly referred to as "Epidemic Dropsy." Since in vitro studies have shown that sanguinarine, an active benzophenanthridine alkaloid of argemone oil, intercalates DNA molecule, the in vivo clastogenic and DNA damaging potential of argemone oil was investigated in mice. Swiss albino mice were intraperitoneally administered 0.5, 1.0, 2.0 and 4.0 ml/kg body wt. of argemone oil to analyze chromosome aberrations and micronucleus test, while 0.25, 0.5, 1.0 and 2.0 ml/kg body wt. were given for alkaline comet assay. The frequencies of chromosomal aberrations and micronucleated erythrocytes formation in mouse bone marrow cells increased in a dose-dependent manner following argemone oil treatment. However, significant induction in chromosomal aberrations (83%) and micronucleated erythrocytes formation (261%) were observed at a minimum dose of 1.0 ml/kg. The results of comet assay revealed DNA damage in blood, bone marrow and liver cells following argemone oil treatment. Olive tail moment (OTM) and tail DNA showed significant increase in bone marrow (35-44%) and blood cells (25-40%) even at a dose of 0.25 ml/kg body wt. of argemone oil. In liver cells, OTM was significantly increased (20%) at a dose of 0.25 ml/kg, while all the comet parameters including OTM, tail length and tail DNA showed significant increase (31-101%) at a dose of 0.5 ml/kg. These results clearly suggest that single exposure of argemone oil even at low doses produces genotoxic effects in mice.     

Genotoxicity and immunotoxic effects of 1,2-dichloroethane in Wistar rats

Dichloroethane is widely used as a solvent, degreasing agent and in a variety of commercial products, and is known for being a ubiquitous contaminant in the environment. Important sources principally include the emissions from industrial processes, improper consumption, storage, and disposal methods. In view of the fact that the mechanism of its genotoxicity has not been satisfactorily elucidated, the acute in vivo toxicological impact is assessed in Rattus norvegicus. A systematic investigation has been made involving the use of conventional methods along with molecular and flow cytometric approaches. The micronucleus and chromosomal aberration frequencies were significantly elevated in bone marrow cells exposed to three concentrations at multiple treatment durations indicating positive time- and dose-response relationships. The mitotic index significantly decreased in similar concentrations in contrast to normal control. Separate studies were performed on blood cells for comet assay. It revealed dichloroethane-induced DNA damage in all exposures readily explainable in a dose- and time-dependent manner. Recent molecular techniques were further employed using leukocytes for the cell apoptosis/cycle and mitochondrial membrane potential employing propidium iodide staining and rhodamine-123, respectively. The effect on mitochondrial membrane permeability, cell cycle phases, and the DNA damage was analyzed through flow cytometry. These indicators revealed dichloroethane treatment decreased the mitochondrial membrane potential, affected the cell cycle, and confirmed the DNA damage, leading to apoptosis of the cells of the immune system responsible for immunotoxic effects of dichloroethane on rat leukocytes.     

五味子水煎剂的遗传毒性研究

背景与目的: 采用小鼠淋巴瘤细胞试验(MLA)和小鼠骨髓微核试验(MNT)研究五味子水煎剂的遗传毒性。 材料与方法: 在MLA中,设五味子0.97、1.94、3.88、7.77 mg/ml (生药)等4个浓度组,在非代谢活化(-S9)和代谢活化(+S9)条件下处理L5178Y细胞3 h;表达2 d,制备基因突变频率平板并培养12 d,计数含大、小突变细胞集落的孔数,计算基因突变频率(MF)和小集落突变百分率(SC%);在MNT中,设3.13、6.25、12.50 g/kg (生药)3个剂量组,每组10只ICR小鼠,雌雄各半,间隔24 h 实施2次小鼠灌胃给予五味子水煎剂,制作骨髓涂片,计数每只小鼠2 000个嗜多染红细胞中含微核的嗜多染红细胞数(MNPCE),计算每组动物嗜多染红细胞微核率。 结果: 在-S9条件下,7.77 mg/ml (生药)浓度组诱发的MF是阴性对照组的2倍以上(P<0.01), SC%随五味子浓度增加而升高。 +S9条件下的各浓度组诱发的MF存在剂量-反应关系,7.77 mg/ml (生药)浓度组的MF明显增加(P<0.01),其MF、SC%与阳性对照组相近;五味子水煎剂各剂量组未显示骨髓抑制作用,所诱发的微核率与阴性对照组比较未见明显增加(P>0.05)。 结论: 五味子水煎剂在+/-S9条件下均可诱发L5178Y细胞tk位点突变并导致染色体损伤,提示对人体具有潜在的遗传毒性;但对小鼠骨髓细胞染色体无损伤,经体内代谢活化后未显示遗传毒作用。     

Cytogenetic Biomonitoring of Road Paving Workers Occupationally Exposed to Polycyclic Aromatic Hydrocarbons

Road pavement workers are exposed to many known carcinogens in their complex occupational environment.The study makes an attempt to investigate exposure to polycyclic aromatic hydrocarbons (PAH) from thebitumen fumes among the road pavement workers engaged in different pavement sites at Coimbatore, TamilNadu and to thereby determine the genotoxic effects associated with it. The study included 36 road pavers and37control subjects with similar mean ages, smoking prevalence and alcohol consumption and was analyzed forDNA damage in blood leucocytes by Micronucleus assay (MN) and the Comet assay. The mean urinary 1-OHPconcentration in road pavers (1.68 ± 0.93) was significantly higher than in controls (0.55 ± 0.42). The results ofMN test and comet assay showed that the mean micronuclei rate in workers was significantly higher than thosein controls (P <0.05). The results of our study indicated that the genetic damage was detectable in road pavingworkers occupationally exposed to bitumen and also demonstrate the high sensitivity of comet assay to assessearly oxidative effects induced by exposure to bitumen fumes at low doses and confirm the suitability of urinary1-OHP as a biomarker of PAH exposure.     

Biomonitoring of Genotoxic Effects Among Shielded Manual Metal Arc Welders

Hexavalent chromium Cr (VI) used in shielded metal arc welding is widely recognized to act as a carcinogen,mutagen and teratogen. The carcinogenic potential of metals is a major issue in defining human health riskfrom exposure. Hence in the present investigation, 66 welders and 60 control subjects with similar mean ages,smoking prevalences and alcohol consumption were enrolled for DNA damage analysis of buccal cells bymicronucleus (MN) and comet assay. Welders showed a significant increase in micronucleated cells comparedto controls and a larger mean comet tail length. The current study thus suggested that chronic occupationalexposure to Cr (VI) during welding could lead to increased level of DNA damage. Understanding the complexityof the relationshipsbetween exposure, basal DNA damage and MN frequencies requires larger scale studies andapplication of complementary biomarkers.