邻苯二甲酸酯类增塑剂的体外细胞毒性评价

邻苯二甲酸酯(Phthalate esters, PAEs)是环境介质中的一类典型的有机污染物。已有研究表明,PAEs具有明显的内分泌干扰毒性,并会对动物和人体的生殖发育与神经系统造成损伤。体外细胞评价模型因具有高通量、测试周期短、成本低和毒性效应易于探明等技术优点,被广泛应用到PAEs毒理学效应的研究中。本文从内分泌干扰毒性、胚胎发育毒性、神经毒性、免疫毒性、遗传毒性以及致癌作用等方面,对PAEs的一些体外细胞毒性评价模型进行了分类和总结,并对其相应的研究进展进行了综述。本文旨在为体外细胞毒性评价模型的有效利用提供借鉴,并对PAEs毒性作用机制的深入研究提供思路和依据。     

2种类型多壁碳纳米管对蛋白核小球藻的毒理研究

碳纳米材料由于其具有优异的性能，得以广泛生产和使用，其不可避免会进入水环境中，对水生生态系统造成潜在影响。多壁碳纳米管(P-MWCNTs)和羟基化多壁碳纳米管(MWCNTs-OH)作为纳米材料的典型代表，应用非常广泛，其潜在的环境效应受到人们越来越多的关注。为此，本文以蛋白核小球藻(Chlorella pyrenoidosa)作为受试生物，通过暴露实验，研究了P-MWCNTs和MWCNTs-OH对蛋白核小球藻的生物学效应。研究结果表明：1)当P-MWCNTs浓度≤10 mg·L-1、MWCNTs-OH≤20 mg·L-1浓度时对蛋白核小球藻生长未造成影响；2)暴露96 h后，当P-MWCNTs≤10 mg·L-1、MWCNTs-OH浓度≤20 mg·L-1时，蛋白核小球藻细胞可溶性蛋白质含量增加，当P-MWCNTs浓度≥20 mg·L-1、MWCNTs-OH浓度≥40 mg·L-1时，2种类型MWCNTs均对蛋白核小球藻造成毒性效应；3)随着2种类型MWCNTs浓度的增加，蛋白核小球藻细胞总抗氧化能力(T-AOC)值减少，蛋白核小球藻细胞丙二醛(MDA)含量显著增加，细胞的健康程度逐渐恶化，细胞结构受到严重损伤；4)MWCNTs-OH比P-MWCNTs具有更好的生物相容性。     

农药致慢性细胞毒性及基因毒性机制研究进展

大量流行病学研究和体内、体外检测分析表明,长期低剂量接触农药可以导致人体细胞和分子损伤,诱导细胞凋亡。农药致细胞及DNA损伤的机制主要与DNA加合物的形成、DNA单链和/或双链的断裂有关。此外,氧化应激参与农药致细胞及DNA损伤的过程,可能成为农药致细胞及DNA损伤的促发因素。从总体上看,其具体分子机制还不十分清楚,有待进一步研究。     

石墨烯纳米材料对哺乳动物的毒性及其作用机制

石墨烯是一种应用广泛的新兴非金属纳米材料，具有独特的电学机械性能、超大的比表面积以及潜在的生物相容性，在材料、电子、能源、光学以及生物医学等领域得到广泛应用。与此同时，石墨烯的环境行为和生物毒性也随之引起日益广泛的关注。本文通过对石墨烯纳米材料的动物毒性、细胞毒性、毒性影响因素和毒性机制等相关研究进展进行总结。石墨烯纳米材料可通过气管滴注、吸入、静脉注射、腹腔注射以及口服等方式进入体内，通过机械屏障、血脑屏障和血液胎盘屏障等积累在肺、肝、脾等部位引起急性或者慢性损伤；目前有关石墨烯毒性机制的研究主要集中于线粒体损伤、DNA损伤、炎性反应、凋亡等终点及氧化应激参与的复杂信号通路，不同石墨烯纳米材料的浓度、尺寸、表面结构和官能团等对石墨烯的生物毒性影响不同。鉴于当前该领域研究的局限性，对石墨烯纳米材料生物毒性研究的发展方向进行了展望，进而为石墨烯材料的安全应用提供理论借鉴和实践参考。     

三氯卡班可以影响肾小管上皮细胞的屏障功能

三氯卡班(TCC)是一种被广泛应用于个人护理用品中的广谱型亲脂性杀菌剂,已在多种环境介质和生物体中检出。因其潜在的环境蓄积、生物累积和生物毒性效应,日益受到学者们的关注。借助TCC对NRK-52E(大鼠肾小管上皮细胞)的毒性暴露实验,通过检测细胞活力、以及与跨膜电阻和紧密连接相关的连接黏附分子1(JAM~(-1),junctional adhesion molecule 1)的蛋白表达水平,研究了TCC潜在的肾脏毒性效应。结果显示,10μmol·L~(-1)TCC处理48 h时培养细胞呈现不规则的集落;10μmol·L~(-1)和20μmol·L~(-1)TCC处理NRK-52E 24 h、48 h和72 h后可以显著抑制细胞生长;3.57μmol·L~(-1)TCC(生长抑制的48 hIC20)处理NRK-52E 48 h可以显著抑制细胞间紧密连接蛋白JAM~(-1)的表达量,并降低跨膜电阻,影响肾脏的屏障功能。本研究的结果能够为进一步揭示TCC对动物的毒害机制、评估其对动物的健康风险提供数据支持。     

垃圾渗滤液中典型内分泌干扰物质(EDCs)细胞毒性分析

垃圾渗滤液的人类健康风险评估日益受到人们重视,也成为研究热点。本文采用一种新型高级氧化技术UV-Fenton处理渗滤液,并用人体乳腺癌细胞(MCF-7)评估处理过程中渗滤液原液以及渗滤液中典型内分泌干扰物质(EDCs)的细胞毒性,对垃圾渗滤液中EDCs的细胞毒性和变化规律进行了研究。结果表明渗滤液中的邻苯二甲酸二丁酯(DBP)、双酚A(BPA)、壬基酚(NP)是产生细胞毒性的主要物质,其毒性大小为DBPBPANP。在同样的氧化降解过程中显示出不同毒性变化规律,通过GC-MS分析,结果显示UV-Fenton过程中产生了大量的中间产物,这也是引起毒性变化的主要原因。实验结果也说明垃圾渗滤液细胞毒性可以通过UV-Fenton过程有效去除。     

不同终点检测5种双酚A类化合物对MCF-7的细胞毒性

双酚A(BPA)及其类似物作为聚碳酸酯的主要合成原料,一直是环境污染的重要问题.其雌激素效应是当今科学研究的重点,而毒性效应研究甚少.为评估环境中BPA类物质的毒性效应,实验采用四唑盐(MTS)比色法检测5种双酚A类化合物对人雌激素受体缺失乳腺癌细胞MCF-7(ER-)增殖活性的影响,2,4-二硝基苯肼法检测细胞乳酸脱氢酶(LDH)露出率,单细胞凝胶电泳(SCGE)检测DNA损伤.用非线性最小二乘法对MTS实验结果拟合剂量-效应曲线,表明所有的剂量-效应曲线(DRC)均能用Weibull或者Logit函数有效表征.以模型估算的半数效应浓度负对数值(pEC50)评估5种化合物的毒性大小依次为:BPB>BPC>TDP>BPE>BPA.LDH检测以及SCGE检测受试化合物对MCF-7(ER-)的损伤作用表明,在效应浓度EC20下,细胞核DNA轻微损伤,细胞增殖受轻微抑制;在效应浓度EC40下,细胞核DNA损伤严重,细胞增殖受到显著抑制,从而导致细胞膜通透性显著改变,使LDH大量露出.     

CHO cell cytotoxicity and genotoxicity analyses of disinfection by-products: An updated review

The disinfection of drinking water is an important public health service that generates high quality, safe and palatable tap water. The disinfection of drinking water to reduce waterborne disease was an outstanding public health achievement of the 20th century. An unintended consequence is the reaction of disinfectants with natural organic matter, anthropogenic contaminants and bromide/iodide to form disinfection by-products (DBPs). A large number of DBPs are cytotoxic, neurotoxic, mutagenic, genotoxic, carcinogenic and teratogenic. Epidemiological studies demonstrated low but significant associations between disinfected drinking water and adverse health effects. The distribution of DBPs in disinfected waters has been well defined by advances in high precision analytical chemistry. Progress in the analytical biology and toxicology of DBPs has been forthcoming. The objective of this review was to provide a detailed presentation of the methodology for the quantitative, comparative analyses on the induction of cytotoxicity and genotoxicity of 103 DBPs using an identical analytical biological platform and endpoints. A single Chinese hamster ovary cell line was employed in the assays. The data presented are derived from papers published in the literature as well as additional new data and represent the largest direct quantitative comparison on the toxic potency of both regulated and emerging DBPs. These data may form the foundation of novel research to define the major forcing agents of DBP-mediated toxicity in disinfected water and may play an important role in achieving the goal of making safe drinking water better.     

Involvement of mitochondrial-mediated caspase-3 activation and lysosomal labilization in acrylamide-induced liver toxicity

Acrylamide (ACR) is a chemical frequently used in both industrial and synthetic processes and may be produced during food processing. ACR at very high concentrations is postulated to exert its toxicity through the stimulation of an oxidative stress. ACR in excessive doses induces the central nervous system, reproduction, and genetic toxicity. However, ACR effects on the liver, a major organ of drug metabolism, have not been adequately explored. In addition, the role of mitochondria in an ACR-mediated hepatotoxicity is still unclear. The aim of this study was to investigate the cytotoxic mechanisms attributed to ACR using isolated rat hepatocytes. Hepatocytes were isolated by the collagenase perfusion method and incubated with an EC50_2hr concentration of ACR for 3 hr. The EC50_{2 hr} of ACR on isolated rat hepatocytes was determined to be 1 mM. Based on our results, hepatocytes cytotoxicity of ACR (1 mM) was mediated by a reactive oxygen species formation and lipid peroxidation. Incubation of hepatocytes with ACR produced rapid hepatocyte glutathione depletion which is another marker of the cellular oxidative stress. ACR cytotoxicity was also associated with mitochondrial injury as evidenced by the decline of mitochondrial membrane potential and lysosomal membrane leakiness. Our results also showed that ACR induced caspase-3 activation, the final mediator of apoptosis signaling. These findings contribute to a better understanding underlying mechanisms involved in ACR hepatotoxicity originating from the oxidative stress and ending in mitochondrial/lysosomal damage and cell death signaling.     

Oxidative stress and biochemical perturbations induced by insecticides mixture in rat testes

The joint action of pyrethroids, lambda-cyhalothrin (LC) in combination with organophosphates, fenitrothione (FNT) on antioxidant defense system and lipid peroxidation biomarkers in rat testes was studied. The results suggest that incubation of testes homogenate with different concentrations of insecticide mixture for different time intervals significantly decreased the activity of antioxidant enzymes, like glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT), and the level of reduced glutathione (GSH). In addition, a significant inhibition in transaminases (AST, ALT), phosphatases (AcP, AlP) activity and protein content were observed. On the other hand, FNT plus LC increased the cellular lipid peroxidation (LPO) level and the activity of lactate dehydrogenase (LDH). In conclusion, the use of insecticides mixture might cause marked oxidative damage in a concentration and time-dependent manner.