染色体畸变核型分析

目的明确染色体畸变核型特点,为人类遗传性疾病的诊治提供参考依据。方法取受检者外周血,进行淋巴细胞培养,常规制备染色体,G显带,镜下计数50个中期分裂相,显微摄影分析10个核型。结果在1065例生殖咨询者中,染色体畸变率为15.7%。其中按畸变类型分类,数目畸变率为9.9%,结构畸变率为2.3%,染色体多态性畸变率为3.5%;按染色体不同分类,常染色体畸变率为11.7%,性染色体畸变率为4.0%。结论人类常染色体易发生畸变,数目畸变是人类染色体畸变的主要类型,结构畸变多发生在常染色体中,染色体多态性以大Y和小Y为主。     

职业危害因素对染色体畸变类型的影响

随着我国经济的迅速发展 ,职业危害及环境污染亦日趋严重 ,铅、砷、镉、锰等金属物质对机体的影响一直是人们关注的问题 ,特别是对人体远期遗传毒性效应 ,更成为众多学者研究的方向[1 3] 。用人外周血淋巴细胞染色体畸变来评价职业危害的远期遗传效应仍是一种难以用其他方法替代的生物技术 ,它灵敏、直观、易于被受试者接受。但职业人群遗传毒性效应监测在职业医学中尚属正在发展的领域 ,如能发现职业危害因素与染色体畸变类型之间的相关性 ,将会对职业危害因素的遗传毒性评价有着非常重要的意义。1　对象与方法1 1　对象　选择某铝业公司…     

司氟沙星CHL细胞体外染色体畸变试验

目的:检测司氟沙星对CHL细胞染色体致畸变作用。方法:用体外方法检测司氟沙星在23.63～189.00μg·mL~(-1)浓度范围内,代谢活化组(含S_9mix)及非活化组(不含S_9mix)CHL 细胞的染色体畸变率。结果:司氟沙星的代谢活化组(含S_9mix)及非活化组(不含S_9mix)的染色体畸变率均低干5%。结论:司氟沙星对CHL 细胞染色体畸变实验结果为阴性。     

不同实验室间染发剂染色体畸变试验结果分析

随着染发剂的广泛使用,其安全性受到人们越来越多的关注[1]。染发剂通常分为氧化型和非氧化型。氧化型染发剂主要成分为显色剂苯胺类染料和氧化剂H2O2,其原理是在氧化剂作用下,苯胺类物质被氧化为染料中间体,然后在偶合剂苯二酚类物质的作用下发生偶合反应产生颜色而染发。其中氧化型染发剂的功效成分是苯胺类衍生物,有报道指出苯胺类衍生物     

PT-141染色体畸变试验

目的采用中国仓鼠肺成纤维细胞(CHL)进行染色体畸变试验,评价PT-141在体外有无致突变性,为临床应用提供安全依据。方法CHL细胞用含质量浓度为20%的小牛血清和双抗(青霉素、链霉素的总浓度分别为100U/ml、100μg/ml)的1640培养液于37℃,恒温培养。(1)细胞毒性试验:采用苔盼蓝染色检测CHL细胞接触PT-14148h的半数细胞生长抑制浓度(IC50),作为剂量选择的依据。(2)染色体畸变试验:以CHL细胞进行加与不加S9的染色体畸变试验。不加S9时,培养瓶内加入4.95ml细胞培养液,50μl受试物,培养24和48h;加S9时,培养瓶内加入4.45ml细胞培养液,50μl受试物,0.5mlS9混合物,培养6h后,弃培养液,PBS洗涤3遍,再加入1640细胞培养液5ml,继续培养至24和48h。分别于收获前4h加入终浓度为0.2μg/ml的秋水仙碱。实验设PT-141高,中,低3个剂量组、并设阴性对照组,阳性对照组分不加S9试验阳性对照组(MMC0.25μg/ml)和加S9试验阳性对照组(CP20μg/ml,作用6h)。收获细胞后,常规低渗、固定、制片和Giemsa染色,每个剂量组油镜下观察分裂中期相细胞100个,记录畸变类型,计算细胞染色体畸变率(%)。各试验剂量均作平行样3份。结果细胞毒性实验显示,PT-141各剂量组,细胞数未发生显著差异,说明PT-141在高剂量5mg/ml未显示毒性反应。故正式实验选择高剂量为5mg/ml、按等比倍量稀释法,中、低剂量分别设定为1mg/ml、200μg/ml。染色体畸变结果显示,阳性对照组的畸变率明显高于阴性对照组,差异具有统计学意义(P<0.01),畸变类型以断裂、缺失、交换为主;CHL细胞接触PT-1412448h,加S9还是不加S9,各剂量组的染色体畸变率与阴性对照组比较差异均无统计学意义(P>0.05)。结论PT-141在体外CHL细胞染色体畸变试验中结果为阴性,在本实验条件下,未发现其具有潜在的致突变性。     

啮齿类动物骨髓微核试验规范化方法介绍及背景数据采集

啮齿类动物骨髓微核试验（in vivo Mammalian Bone Marrow Micronucleus Test）是临床前药物遗传毒性研究标准组合试验之一,在医学、公共卫生、食品和药物安全性评价等领域有巨大应用前景。在GLP条件下确立标准化试验方法和条件,积累一定的背景数据范围,可有效确保试验系统的可靠性,为数据分析提供有力依据。以国家药物安全评价监测中心2007－2015年开展的小鼠及大鼠骨髓微核试验背景数据采集为例,介绍啮齿类动物骨髓微核试验规范化采集方法。     

威麦宁对中国仓鼠卵巢细胞染色体的畸变作用

威麦宁是从中草药金荞麦中提取的单宁化合物,民间用于治疗肺脓疡。抗癌实验表明,该药有明显的抑制实验动物Lewis肺癌、U14宫颈癌及S180肉瘤等作用,在体外还能明显抑制小鼠白血病细胞(P388)和人胃腺癌细胞(SGC7901)对H~3-TdR的掺入。目前该药已用于临床,为了观察该药是否具有损伤染色体的效应,我们用中国     

膀胱癌实体瘤染色体畸变的研究

本文用直接法分析11例膀胱癌的细胞遗传学改变。其染色体数目异常范围为2n-4n。其中非浸润性的为2n,浸润性的为2n-4n,并具有标记染色体。染色体结构异常主要为缺失;易位和等臂染色体。作者认为这些改变与膀胱癌的发生、发展有密切的关系。     

外周血中单个细胞染色体畸变的临床意义

目的：评价外周血中单个细胞染色体畸变的临床意义。方法：常规取外周血培养,制备染色体G显带标本,镜下核型分析,以每30-100个分裂相中发现1个异常染色体核型作为单个细胞染色体结构畸变的诊断标准。结果：21例外周血单个细胞染色体畸变个体具有生育异常、性发育异常、智力低下等临床表现;单个细胞染色体畸变的类型较多,有平衡易位、倒位、缺失、重复、单体型等,涉及的染色体种类也多,包括2、3、6、7、8、9、10、14、18、21等常染色体和性染色体。结论：外周血单个细胞染色体畸变与患者临床症状的出现有一定联系。     

精安胶囊对小鼠睾丸精母细胞染色体畸变的影响

精安胶囊是一种临床前研究的新药 ,可用于治疗精子数量过少、精子活力不足为表现的男性不育症。为评价其对实验动物睾丸精母细胞染色体畸变的影响 ,了解是否具有致突变作用 ,预测其遗传危害性 ,我们按有关的检测方法 ,进行小鼠睾丸精母细胞染色体畸变试验 ,为临床安全使用该产品提供参考依据。1　材料与方法1 1　动物　ＮＩＨ小鼠由广东省医学实验动物中心提供 (合格证号 :2 0 0 0Ａ0 2 5 ) ,体重为 2 5～ 33ｇ ,实验前观察 1周 ,经检疫合格。1 2　试剂　精安胶囊 (由中山市三才医药集团公司提供 ,批号 :0 0 0 30 1)、丝裂霉素Ｃ(浙江海正制…     

螺旋藻片对小鼠睾丸染色体致畸变实验研究

目的探讨螺旋藻片的毒性作用。方法以4.0、2.0、1.0g.kg-1BW（体重Body Weight）剂量的螺旋藻片连续给小鼠灌胃5d,取小鼠两侧睾丸,制备小鼠睾丸生殖细胞染色体标本。结果各剂量组小鼠睾丸染色体断片、易位、畸变细胞率、常染色体单价体、性染色体单价体与溶剂对照组比较无显著性差异（P〉0.05）,而阳性对照组断片、畸变细胞率、常染色体单价体、性染色体单价体与溶剂对照组比较有极显著性差异（P〈0.01）。结论螺旋藻片各剂量组对小鼠睾丸生殖细胞无染色体畸变作用。     

人参皂苷Rd对中国仓鼠肺细胞染色体畸变作用

目的研究人参皂苷Rd致中国仓鼠肺细胞（Chinese hamster lung cells,CHL）染色体畸变的作用。方法细胞计数法测定人参皂苷Rd对CHL细胞的半数抑制浓度（IC50）,根据IC50设立不同剂量组,进行染色体畸变试验,分别观察人参皂苷Rd染毒6、24h及加S9后染毒6hCHL细胞染色体的数目及结构变化,进行染色体畸变分析。结果人参皂苷Rd染毒6、24h及加S9后染毒6hCHL细胞染色体畸变为阴性。结论在本试验条件下,人参皂苷Rd不能引起CHL细胞染色体产生畸变。     

宫炎平片的遗传毒性试验研究

目的在体外条件下研究宫炎平片(GYP)是否具有遗传毒性,为临床用药安全提供依据。方法对GYP设不同剂量组,选用Ames试验、体外CHL细胞染色体畸变试验和小鼠骨髓嗜多染红细胞微核试验进行遗传毒性试验。结果Ames试验各组平皿均未见细菌毒性表现,结果为阴性。CHL试验中24 h后采样以及48 h后采样,所有剂量的细胞染色体畸变率均未显著增高,GYP无抑制有丝分裂或诱导染色体数目畸变的能力,微核试验结果为阴性无统计学意义(P>0.05)。结论综合以上3个试验结果,认为在实验条件下,GYP无遗传毒性。     

补血益母丸遗传毒性研究

目的 对补血益母丸干膏粉进行遗传毒性试验,为临床安全用药提供依据。方法 采用组氨酸营养缺陷型鼠伤寒沙门氏菌TA97a、TA98、TA100、TA102、TA1535进行细菌回复突变（Ames）试验,采用中国仓鼠肺成纤维（CHL）细胞进行体外染色体畸变试验,采用ICR小鼠进行骨髓细胞微核试验综合评估补血益母丸干膏粉的遗传毒性。其中,Ames试验设50、150、500、1 500、5 000 μg·皿^-1 5个剂量;体外细胞染色体畸变试验设125、250、500 μg·mL^-1 3个剂量;小鼠骨髓细胞微核试验设500、1 000、2 000 mg·kg^-1 3个剂量,每天给药1次,连续给药3 d。结果 在代谢及非代谢活化条件下（＋S9/-S9）,Ames试验结果 显示,补血益母丸干膏粉对各菌株均无明显或可重复的诱变性及抑菌性;体外CHL细胞染色体畸变试验结果显示,补血益母丸干膏粉对CHL细胞染色体结构畸变率未见有意义的升高;小鼠骨髓细胞微核试验结果显示,补血益母丸干膏粉对ICR小鼠骨髓细胞微核率无明显影响。结论 补血益母丸干膏粉未见潜在的遗传毒性。     

银参胶囊遗传毒性研究

目的探讨银参胶囊的遗传毒性。方法选用SPF级健康ICR小鼠,通过Ames试验、小鼠骨髓细胞微核试验、小鼠睾丸染色体畸变试验等遗传毒性试验验证银参胶囊的安全性。结果 Ames试验中,银参胶囊在8~5 000μg/皿剂量范围内,无论是否加入哺乳动物肝脏微粒体酶(S9),鼠伤寒沙门菌TA97,TA98,TA100,TA102等4株菌的回复突变菌落数均未出现剂量依赖性增加;微核试验中,2 500,5 000,10 000 mg/kg剂量组均未见骨髓中含微核的嗜多染红细胞数增加;小鼠睾丸染色体畸变试验中,药物质量分数为2 500,5 000,10 000 mg/kg时,细胞的染色体畸变率均未出现剂量依赖性增加。结论银参胶囊未显示致突变作用,可初步判定其在遗传毒性方面是安全的。     

The in vivo genotoxic effects of carvacrol and thymol in rat bone marrow cells

The aim of this study was to investigate the in vivo genotoxic effects of carvacrol and thymol in bone marrow cells of rats. In the present study, both carvacrol (10, 30, 50, and 70 mg/kg b.w.) and thymol (40, 60, 80, and 100 mg/kg b.w.) significantly induced the structural and total chromosome abnormalities (CA) for all treatment periods (6, 12, and 24 h) when compared with control in bone marrow cells of rats intraperitonally administered. Both carvacrol and thymol showed similar effects with the positive control urethane on induction of the percentage of structural and total CA at the highest concentrations except the effects of carvacrol for 6 h treatment (70 mg/kg b.w. and 100 mg/kg b.w., respectively). In addition, carvacrol induced the numerical CA at all concentrations when compared to control and at two highest concentrations (50 and 70 mg/kg b.w.) when compared to solvent control. Thymol also induced the numerical CA especially at the highest concentration (100 mg/kg b.w.) for all treatment periods. It was shown that there was a dose-dependent effect on induction of structural, numerical and total CA for both carvacrol and thymol. Carvacrol and thymol decreased the mitotic index (MI) in all the concentrations and treatment times when compared with control. Carvacrol showed the similar effects with EC on decreasing the MI at 70 mg/kg b.w. for 6 h, at 30 and 50 mg/kg b.w. for 12 h and at all concentrations for 24 h treatment periods. Thymol also showed a similar effect with urethane (ethyl carbamate, EC) on decreasing the MI at 60, 80, and 100 mg/kg b.w. for 6 h and at all concentrations for 24 h treatment periods. Test substances decreased the MI in a dose-dependent manner.     

Genotoxicity of motorcycle exhaust particles in vivo and in vitro.

We studied the genotoxic potency of motorcycle exhaust particles (MEP) by using a bacterial reversion assay and chromosome aberration and micronucleus tests. In the bacterial reversion assay (Ames test), MEP concentration-dependently increased TA98, TA100, and TA102 revertants in the presence of metabolic-activating enzymes. In the chromosome aberration test, MEP concentration-dependently increased abnormal structural chromosomes in CHO-K1 cells both with and without S9. Pretreatment with antioxidants (alpha-tocopherol, ascorbate, catalase, and NAC) showed varying degrees of inhibitory effect on the MEP-induced mutagenic effect and chromosome structural abnormalities. In the in vivo micronucleus test, MEP dose-dependently induced micronucleus formation in peripheral red blood cells after 24 and 48 h of treatment. The increase of micronucleated reticulocytes induced by MEP was inhibited by pretreatment with alpha-tocopherol and ascorbate. The fluorescence intensity of DCFH-DA-loaded CHO-K1 cells was increased upon the addition of MEP. Our data suggest that MEP can induce genotoxicity through a reactive oxygen species-(ROS-) dependent pathway, which can be augmented by metabolic activation. Alpha-tocopherol, ascorbate, catalase, and NAC can inhibit MEP-induced genotoxicity, indicating that ROS might be involved in this effect.     

The genotoxic and antigenotoxic potential of the methanolic root extract of Glycyrrhiza glabra L. on human peripheral blood lymphocytes

Glycyrrhiza glabra L. (licorice) is one of the most important medicinal plants, which is widely used throughout the world both in traditional and contemporary medical industries. This study was undertaken to investigate the potential genotoxic activity of G. glabra methanolic root extract, and its possible antigenotoxic properties against mitomycin C (MMC)-induced DNA damage in in vitro chromosome aberrations (CAs) and cytokinesis-block micronucleus (CBMN) assays in human peripheral blood lymphocytes (PBLs). Lymphocytes were treated with 25, 50, and 100?µg/ml G. glabra methanolic root extract alone as well as in combination with MMC (0.1?µg/ml) for 24 and 48?h treatment periods. It was found that there were no statistically significant differences between the negative control and the groups treated with all concentrations of G. glabra root extract of alone (p?>?0.05), demonstrating the absence of genotoxic effects at both 24 and 48?h treatment periods. Besides, the co-treatment of G. glabra methanolic root extract and MMC significantly decreased the percentage of structural CAs and MN formation when compared with the culture treated with MMC alone (p?G. glabra versus MMC. We can state that this extract acts as an antagonist and markedly decreased MMC-induced cytogenotoxicity. In conclusion, the present results demonstrate that in the tested experimental conditions, G. glabra methanolic root extract is not genotoxic in cultured human PBLs and has also antigenotoxic activity against MMC, which is widely used in chemotherapy against cancer.     

In vitro genotoxic and cytotoxic effects of some paraben esters on human peripheral lymphocytes

Parabens (PBs) are p-hydroxybenzoic acid ester compounds commonly employed as antimicrobial preservatives, mainly in food, cosmetic, and pharmaceutical products. The aim of the present study was to investigate the genotoxic and cytotoxic effects of some paraben esters (butyl paraben, propyl paraben, isobutyl paraben, and isopropyl paraben) on human peripheral lymphocytes, using in vitro sister chromatid exchange (SCE), chromosome aberration (CA), and cytokinesis-block micronucleus (CBMN) tests. Lymphocyte cultures were treated with four concentrations of PBs (100, 50, 25 and 10?µg/mL) for 24 and 48?h. Paraben esters significantly induced MN formations as compared to solvent control. Furthermore, butyl paraben and propyl paraben increased MN formations a concentration-dependent manner at 24 and 48?h. PBs increased the CA at 24 and 48?h. However, this increase was not meaningful for butyl paraben and isopropyl paraben at 48?h when compared with solvent control. Butyl, isobutyl, and isopropyl paraben significantly increased the SCE at 24 and 48?h. However, propyl paraben did not induce SCE meaningfully in both treatment periods. A significant decrease in the cytokinesis-block proliferation index and mitotic index was observed in cells exposed to all concentrations of PBs at 24 and 48?h. However, proliferation index was not affected at all concentrations of PBs after 24?h treatment, although it was decreased at the highest concentration of PBs at 48?h. It is concluded that all of the paraben esters used in this study have highly genotoxic and cytotoxic effects on human lymphocytes cells in vitro.     

A New Interpretation of Avian and Mammalian Reproduction Toxicity Test Data in Ecological Risk Assessment

The long-term risks of pesticides to wildlife in the EU currently are assessed by comparing the lowest no-observed-effect concentration (NOEC) determined from the suite of endpoints measured in existing avian and mammalian laboratory reproduction tests with estimated exposure concentrations by calculating Toxicity to Exposure Ratios (TERs). Regulatory authorities experience difficulties when assessing long-term risks because of the lack of accepted methods to improve the ecological realism of exposure and toxicity estimates and understand risks at a population level. This paper describes an approach for interpreting existing avian and mammalian toxicity test data that divides breeding cycles into several discrete phases and identifies specific test endpoints as indicators of direct pesticide effects possible at each phase. Based on the distribution of breeding initiation dates for a species of concern and the dates of pesticide applications, this approach compares the phase-specific toxicity endpoint with the expected pesticide exposure levels during each of the breeding phases. The fate of each breeding attempt is determined through a series of decision points. The cumulative reproductive response of individuals in a breeding population based on this decision framework provides a means of examining the estimated risks over the course of the breeding season and deriving an overall metric of the impact of the pesticide on reproduction. Research needed to further improve the approach is discussed.