取代苯对人体细胞的定量结构—遗传毒性研究

通过微核实验,测定了 36 种取代苯类化合物对人体外周血淋巴细胞的遗传毒性;并构建了遗传毒性与分子结构参数之间的 QSAR 模型.结果表明,有 34 种化合物显著地导致了微核的产生,具有明显的遗传毒性;遗传毒性的大小与分子结构描述符辛醇-水分配系数(MlogP)、x 轴主惯性矩(Principalx)、γ 极化率[Polar(γ)]等存在良好的结构-活性相关关系,所建模型的相关系数 R² =0.718,具有较高的预测能力,可用来预测取代苯类化合物的遗传毒性.     

室内空气高浓度苯系物的蚕豆根尖遗传毒性研究

蚕豆根尖微核(micronucleus,MCN)检测技术是一项检测水环境致突性因素的成熟技术,该研究采用敏感的松滋青皮蚕豆为材料,在密闭容器中模拟室内空气的高浓度苯系物污染,对蚕豆根尖进行染毒,然后用显微镜观察蚕豆根尖细胞中的微核.通过对实验结果进行污染指数(PI)和t检验分析表明:在所有实验浓度下,苯、甲苯和二甲苯都对蚕豆根尖细胞产生了遗传毒害效应;对受试物质量浓度和微核率进行一元线性回归分析后得到线性方程,表明二者间存在线性关系.该实验结果还表明,利用蚕豆根尖微核检测技术检测室内空气中较高浓度的苯系物污染是完全可行的.      

五氯酚钠与二英对人外周血淋巴细胞的影响

将五氯酚钠(Na-PCP)与二(噁)英(2,3,7,8-TCDD)作为受试物,观察了人外周血淋巴细胞的彗星率和微核率.结果显示:Na-PCP与二噁英各质量浓度组的彗星率与微核率均比阴性对照组有明显的增高(P＜0.001),而且随着质量浓度的增加而增高,呈明显的剂量-效应关系;阴性对照组与助溶剂对照组没有明显差异(P＞0.05);Na-PCP与二(噁)英(2,3,7,8-TCDD)会对人外周血淋巴细胞的DNA造成损伤,而且随着质量浓度的增加,其对DNA的损伤将更加严重;Na-PCP对人外周血淋巴细胞造成的损伤为联合毒性所致.      

Detection of environmental clastogens and aneugens in human fibroblasts by cytokinesis-blocked micronucleus assay associated with immunofluorescent staining of CENP-A in micronuclei

The cytokinesis-blocked micronucleus (CBMN) assay, in combination with fluorescent in situ hybridization (FISH) of human pan-centromeric DNA probes, or with CREST antibodies that specifically stain kinetochore proteins, is widely used on several cell types. It distinguishes micronuclei containing one or several whole chromosomes, which are positively labeled (centromere positive micronucleus, C+MN, due to aneugenic effect), or acentric chromosome fragments, which are unlabeled due to the absence of centromere (centromere negative micronucleus, C−MN, due to clastogenic effect). However, the very slight level of the centromeric signals obtained with the FISH technique on primary human fibroblasts, a cell type commonly used in environmental genetic toxicology, leads to great difficulties in distinguishing C+MN and C−MN. Furthermore, the CREST technique may lead to inappropriate results particularly with regards to variations in antibody composition between patient sera. Our results show that the in vitro CBMN, in combination with immunofluorescence staining of CENP-A (centromere protein A), efficiently screens genotoxicants for their ability to induce clastogenic and/or aneugenic effects. We propose the in vitro CBMN assay in combination with immunofluorescence staining of CENP-A as a suitable tool in environmental genotoxicity testing of primary human fibroblasts.     

Evaluation of the genotoxic and cytochrome P450 monooxygenase‐inhibitory potential of dicuran on procaryotic and eucaryotic test systems

Abstract

The effect of the herbicide Dicuran 500 FL (formulated product) on the phenotypical and genotypical changes in procaryotic and eucaryotic organisms was investigated using short‐term tests for detecting genotoxins. Since pesticides discharged in the water environment can modulate the mixed‐function monooxygenases (MFO) detoxification system of water organisms, the in vivo and in vitro effects of Dicuran on hepatic cytochrome P450 (cyt P450) monooxygenase activities were also examined in juvenile carp (Cyprinus carpio L.). By measuring the activities of MFO in experimental carp exposed to Dicuran an attempt was made to establish whether Dicuran could be bioactivated by MFO into ultimate mutagens. Our results on the bacterial strains Salmonella typhimurium TA100 and TA98 show that Dicuran does not possess either mutagenic or premutagenic characteristics. The micronucleus test on the erythrocytes of experimental carp did not establish any clastogenic effect either. However, Dicuran significantly inhibited the MFO activity of 7‐ethoxyresorufin‐O‐deethylase (EROD) and benzo[a]pyrene monooxygenase (BaPMO) in the liver of experimental carp in vitro, as well as in in vivo conditions. These findings demonstrate the potentially damaging effect of Dicuran on the xenobiotic metabolizing enzyme systems of fish, and suggest the applicability of described methods for the prediction of the ecotoxicological significance of the presence of pesticides in the water environment.     

五氯苯酚的生态毒性效应及其遗传毒性

为评价环境内分泌干扰物——五氯苯酚对土壤生态系统动植物的生态毒性效应,检测了五氯苯酚对8种作物种子的萌发和根伸长的抑制作用以及对赤子爱胜蚓(Eisenia fetida)的急性毒性作用;并运用小麦根尖细胞微核实验和赤子爱胜蚓体细胞核的彗星实验,检测了五氯苯酚的遗传毒性效应.结果表明,五氯苯酚在一定浓度范围内对作物种子的...     

三种洗涤剂对黑眶蟾蜍蝌蚪生长发育的影响

研究了三种家用洗涤剂对黑眶蟾蜍(Bufo melanostictus Schneider)蝌蚪生长发育的影响。结果表明,三种洗涤剂对蝌蚪均有毒害作用.在急性实验中,洗衣粉和洗洁精对蝌蚪的72h半致死浓度LC50分别为52.7mg/L和51.4mg/L;在慢性实验中,对蝌蚪外观形体的影响主要表现为身体畸形和皮肤透明,而对蝌蚪红细胞的影响表现在其微核率与浓度和时间有一定的相关性。     

淮河流域安徽段水体成组生物毒性评价

在淮河流域安徽段某区域采集了3个地表水样和12个地下水样,通过大型溞急性毒性(活动抑制)、微核及SOS/umu试验,分析了这些水样的急性毒性及遗传毒性。结果表明,急性毒性测试中,该区域地表水及大部分地下水的急性毒性均未超过US EPA废水排放毒性的控制要求(0.3 TU),有2个位点的地下水样毒性当量为0.31 TU,超过限值;经t-test分析,地表水的急性毒性显著高于地下水。SOS/umu检测中,2个地表水样和7个地下水样的结果呈阳性,表现出DNA损伤效应,其诱导率IR在(2.20±0.063)~(3.36±0.067)之间,对应的致癌风险P基本处在10-6~10-7水平。微核检测结果表明,3个地表水样具有较严重的染色体损伤效应,9个地下水样表现为阴性。总之,该区域地表水急性毒性及遗传毒性相对较高;部分浅层地下水也存在一定程度的急性毒性和遗传毒性,致癌风险处在可接受范围,但仍可能对周围居民的健康产生潜在威胁;而深层地下水没有检测到任何毒性效应。研究为周边居民饮水安全和人体健康提供了基础信息。