Tetrabromobisphenol A (TBBPA): A controversial environmental pollutant

Tetrabromobisphenol A (TBBPA) is one of the most widely used brominated flame retardants and is extensively used in electronic equipment, furniture, plastics, and textiles. It is frequently detected in water, soil, air, and organisms, including humans, and has raised concerns in the scientific community regarding its potential adverse health effects. Human exposure to TBBPA is mainly via diet, respiration, and skin contact. Various in vivo and in vitro studies based on animal and cell models have demonstrated that TBBPA can induce multifaceted effects in cells and animals, and potentially exert hepatic, renal, neural, cardiac, and reproductive toxicities. Nevertheless, other reports have claimed that TBBPA might be a safe chemical. In this review, we re-evaluated most of the published TBBPA toxicological assessments with the goal of reaching a conclusion about its potential toxicity. We concluded that, although low TBBPA exposure levels and rapid metabolism in humans may signify that TBBPA is a safe chemical for the general population, particular attention should be paid to the potential effects of TBBPA on early developmental stages.     

Inorganic arsenic: A non-genotoxic carcinogen

Inorganic arsenic induces a variety of toxicities including cancer. The mode of action for cancer and non-cancer effects involves the metabolic generation of trivalent arsenicals and their reaction with sulfhydryl groups within critical proteins in various cell types which leads to the biological response. In epithelial cells, the response is cell death with consequent regenerative proliferation. If this continues for a long period of time, it can result in an increased risk of cancer. Arsenicals do not react with DNA. There is evidence for indirect genotoxicity in various in vitro and in vivo systems, but these involve exposures at cytotoxic concentrations and are not the basis for cancer development. The resulting markers of genotoxicity could readily be due to the cytotoxicity rather than an effect on the DNA itself. Evidence for genotoxicity in humans has involved detection of chromosomal aberrations, sister chromatid exchanges in lymphocytes and micronucleus formation in lymphocytes, buccal mucosal cells, and exfoliated urothelial cells in the urine. Numerous difficulties have been identified in the interpretation of such results, including inadequate assessment of exposure to arsenic, measurement of micronuclei, and potential confounding factors such as tobacco exposure, folate deficiency, and others. Overall, the data strongly supports a non-linear dose response for the effects of inorganic arsenic. In various in vitro and in vivo models and in human epidemiology studies there appears to be a threshold for biological responses, including cancer.     

磷酸化蛋白质组学技术的发展及其在环境毒理研究中的应用

磷酸化修饰是蛋白质最主要的翻译后修饰形式之一,磷酸化蛋白质组学从整体上观察细胞或组织中磷酸化修饰的状态及其变化,为探讨药物刺激和环境应激下生物体受损的生物学过程提供新的视角.针对磷酸化蛋白质组学技术的发展以及其在环境毒理研究中的应用展开综述.首先,从磷酸化肽富集、磷酸化蛋白的鉴定和磷酸化位点的预测、定量磷酸化蛋白质组学研究3个方面对磷酸化蛋白质组学技术的研究内容和分析策略进行了概述.在此基础上,按照离体实验、活体实验以及毒性作用通路分析3部分对磷酸化蛋白质组学在环境毒理研究中的应用进行了详细阐述.最后,总结了目前磷酸化蛋白质组学研究的不足,并有针对性地提出了磷酸化蛋白质组学在环境毒理研究中的发展方向.     

Neural stem cell-based in vitro bioassay for the assessment of neurotoxic potential of water samples

Intensive agriculture activities, industrialization and growing numbers of wastewater treatment plants along river banks collectively contribute to the elevated levels of neurotoxic pollutants in natural water reservoirs across Europe. We established an in vitro bioassay based upon neural stem cells isolated from the subventricular zone of the postnatal mouse to evaluate the neurotoxic potential of raw wastewater, treated sewage effluent, groundwater and drinking water. The toxic potential of water samples was evaluated employing viability, proliferation, differentiation and migration assays. We found that raw wastewater could reduce the viability and proliferation of neural stem cells, and decreased the neuronal and astrocyte differentiation, neuronal neurite growth, astrocyte growth and cell migration. Treated sewage water also showed inhibitory effects on cell proliferation and migration. Our results indicated that relatively high concentrations of nitrogenous substances, pesticides, mercuric compounds, bisphenol-A, and phthalates, along with some other pollutants in raw wastewater and treated sewage water, might be the reason for the neuroinhibitory effects of these water samples. Our model successfully predicted the neurotoxicity of water samples collected from different sources and also revealed that the incomplete removal of contaminants from wastewater can be problematic for the developing nervous system. The presented data also provides strong evidence that more effective treatments should be used to minimize the contamination of water before release into major water bodies which may be considered as water reservoirs for human usage in the future.     

双酚A体外类雌激素活性评价及其作用机制的初步研究

采用体外MCF-7细胞增殖试验检测了双酚A(BPA)的类雌激素活性，并用生长曲线分析、细胞周期分析、他奠昔芬拮抗试验和凋亡检测对其作用机制进行了初步探讨。结果显示BPA有明显刺激MCF-7细胞增殖的类雌激素活性；细胞周期分析BPA组细胞增殖指数均明显高于溶剂对照组；BPA刺激MCF-7细胞增殖的类雌激素活性可被Tam拮抗：BPA能明显抑制MCF-7细胞凋亡的发生。结果提示BPA刺激MCF-7细胞增殖的类雌激素活性作用机制可能是BPA与雌激素受体结合后，影响细胞增殖及细胞凋亡过程，从而产生一系列生物效应。     

毒性有机物BPA与普通小球藻的相互影响特性研究

考察了不同浓度双酚A(BPA)对普通小球藻(Chlorella vulgaris)生长特性的影响,以及普通小球藻生长过程对BPA的去除效能.研究表明,低浓度BPA(0~20 mg·L-1)对普通小球藻生长具有促进作用,而高浓度BPA(20~50 mg·L-1)对普通小球藻生长具有抑制作用,且抑制效应与BPA浓度呈正相关关系.低剂量BPA(<20 mg·L-1)对叶绿素含量并无明显的影响,高剂量BPA(>20 mg·L-1)造成叶绿素含量降低.在BPA初始浓度2~50 mg·L-1的范围内,普通小球藻对其都有一定的去除效能,单位普通小球藻对BPA去除速率与其初始浓度呈正相关关系.BPA投加量为50 mg·L-1时,BPA去除速率最大,且最大速率出现于延滞期与对数期之间.     

铁改性掺氮碳纤维活化过一硫酸盐降解双酚A

通过静电纺丝制备了Fe和N掺杂改性的碳纳米纤维（Fe-N-CNF）,研究了该催化剂活化过一硫酸盐（PMS）降解双酚A（BPA）的性能.以聚丙烯腈为前驱体通过添加FeCl₃、尿素、NH₄Cl、均苯四甲酸二酐等配制溶胶进行静电纺丝,预氧化并高温碳化后获得Fe-N-CNF,研究了Fe-N-CNF投加量、PMS投加量、溶液初始pH对BPA降解效果的影响.结果表明,当Fe-N-CNF投加量为1 g·L^-1,PMS投加量为2 mmol·L^-1,初始pH为5时,30 min内对初始浓度为20 mg·L^-1 BPA的降解率可达100%.自由基淬灭实验和电子自旋共振波谱（ESR）分析证明,该体系中起主要作用的活性氧物种是O₂^·-和¹O₂.同时研究了Fe-N-CNF/PMS体系对多种有机污染物的降解效果.     

被动式采样器与原位鱼体暴露用于监测水体Ah受体效应的比较研究

采用被动式采样器SPMD结合H4ⅡE鼠肝癌细胞离体EROD测试的方法来评价水体中Ah受体效应物质的污染水平.以多环芳烃(PAHs)为目标化合物,在太湖梅梁湾地区选取了5个站点,同时放置SPMD采样器和笼养鲫鱼进行32 d的现场原位暴露实验,然后对SPMD样品提取液进行化学分析和离体EROD测试,对鱼肌肉样进行化学分析和对肝胰脏样进行活体EROD测试.结果表明,随着暴露时间的延长,SPMD样品提取液诱导EROD酶的能力逐渐增强,经过32 d暴露的SPMD样品的提取液其诱导的EROD酶活相当于TCDD的毒性当量值为3.8～6.2 pg/g,而且根据化学分析结果计算的PAHs相当于TCDD的毒性当量值与离体生物测试结果之间相关性很好(R²=0.88),说明PAHs是引起该地区水体EROD效应的一个重要诱导因子;根据化学分析结果而配制的模拟样品的离体EROD测试结果表明,多环芳烃类物质对梅梁湾地区水体Ah受体效应的贡献约为40%～50%.研究还发现,SPMD提取液离体EROD测试结果与同时暴露的鱼体肝胰脏的活体EROD测定结果之间也存在较好的相关性(R²=0.62).因此认为,SPMD结合离体EROD测试的方法能够很好的用于评价水体中Ah受体效应物质的污染水平,并能够用于揭示特定化合物与相应的生物效应之间的定量关系.     

Embryonic and fetal globins are expressed in adult erythroid progenitor cells and in erythroid cell cultures

The understanding of human hemoglobin ontogeny during development is of biological and clinical importance. Molecular and immunocytological techniques were used to study the expression of embryonic zeta (ζ), epsilon (ε), and fetal gamma (γ) globin genes in newborn cord blood, peripheral blood from men, pregnant and non-pregnant women, and in vitro mononuclear cell cultures. We have shown that embryonic and fetal globin mRNA and peptides are expressed in cultured erythroid cells and in circulating blood cells from newborns, adult non-pregnant women and from men. The findings suggest that during erythroid cell differentiation in newborns and adults, there is a transient recapitulation of sequential globin chain expression as found during embryonic and fetal development. Furthermore, these findings underscore the need for caution in using embryonic and fetal globin chains as markers to identify erythroid cells of fetal origin in maternal circulation for prenatal diagnosis. Copyright © 2001 John Wiley & Sons, Ltd.     

我国淡水水体中双酚A(BPA)的生态风险评价

双酚A(BPA)对水生生物有多种毒性效应,其中雌激素作用尤为显著.本研究依据BPA对水生生物是否有雌激素效应,把数据分为两类,并通过商值法、安全阈值法、商值概率法以及联合概率曲线法评价了我国淡水水体中BPA对水生生物的风险程度.结果表明,采用4种评价方法得出的结果相近,我国淡水生物对BPA的雌激素效应较BPA对水生生物的其他毒性作用更为敏感;安全阈值法较商值法、商值概率法、联合概率风险评价法误差较小,评价结果更为可信.用安全阈值法评价结果表明,以BPA的雌激素作用为效应终点时,水生生物长期暴露于我国淡水环境中,我国64.70%的淡水水体有导致超过5%的水生生物受到雌激素作用的风险,BPA安全浓度上限为15.72 ng·L-1;而水生物种短期暴露于我国淡水环境中,我国20.43%的淡水水体有导致超过5%的我国淡水生物受BPA雌激素作用的干扰,此时BPA安全浓度上限为2.24×102ng·L-1.     

处理BPA模拟废水的SBR工况参数对污泥有机毒性的影响研究

在处理双酚A(BPA)模拟废水的序批式活性污泥系统(SBR)反应器中,保持进水COD含量均为300 mg·L-1左右,通过改变水力停留时间HRT从12~8 h,污泥龄SRT从20~10 d,考察污泥有机毒性和其他水质指标的变化.试验分析了空白组和40 mg·L-1初始浓度BPA对照组在不同工况条件下周期末出水COD值、污泥有机毒性分布规律以及稳定期单周期内COD值和污泥有机毒性的变化趋势.结果表明,缩短水力停留时间和污泥龄有利于活性污泥降解BPA,并消减稳定期污泥的有机毒性;出水COD稳定在50 mg·L-1左右,且水相和泥相均无BPA残留.在应用PCR-DGGE技术分析SBR系统内微生物菌群多样性和不同样品间的相似性过程中,得出污泥总毒性抑制率与微生物多样性呈负相关性关系,进水成分的不同和运行参数改变是导致污泥总毒性差异的主要原因.     

Determination of estrogenic activity in the river Chienti (Marche Region, Italy) by using in vivo and in vitro bioassays

Environmental estrogen-like compounds (i.e. xenoestrogens) are a variety of pollutants, ranging from synthetic to natural occurring molecules, that are found in surface and waste waters over a wide range of concentrations. In aquatic environment, the overall estrogenic activity is often due to the presence of a mixture of chemicals and their degraded products which can induce synergistic effects. Current strategies for monitoring estrogen-like chemicals are based on the use of a battery of in vivo and in vitro ecotoxicological tests. In this regard, the aim of the present work was to carry out a bio-monitoring study for testing estrogenicity of the Chienti river (Marche Region, Italy) by using both an E-screen and a vitellogenin (Vtg) induction assay in juvenile goldfish. Three sites were used for analysis, localized at the mouth (sampling point 1), in the middle (sampling point 2) and at the origin (sampling point 3) of Chienti river. For most of the water samples (i.e. samples collected at sampling points 2 and 3), clear estrogenic activity was detected in the E-screen assay suggesting different proliferation activities in function of the collecting site. In contrast, the Vtg ELISA demonstrated that water samples collected from each sampling point were estrogenic. Overall, we showed for the first time that the estrogenic activities in water samples from the Chienti river were significant in both in vivo and in vitro; we also observed a different sensitivity between bioassays.     

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.     

微小小环藻对双酚A的富集与降解

对深圳福田红树林优势藻种微小小环藻(Cyclotella caspia)对BPA的生物富集与降解进行了研究.结果显示,微小小环藻对BPA具有较弱的富集能力,当BPA浓度为6.00、8.00、10.00 mg·L-1时,藻细胞在16d时分别达到最大富集量0.01、0.13、0.14 mg·g-1和最大生物富集系数(BCF)0.15%、1.18%、0.16%.微小小环藻对BPA亦具有一定的降解能力,浓度为6.00、8.00、10.00 mg·L-1的BPA在16d内分别有22.39%、36.44%和10.28%被藻降解,日平均生物降解量分别为0.08、0.18和0.06 mg·L-1.     

Role of nitric oxide in the genotoxic response to chronic microcystin-LR exposure in human–hamster hybrid cells

Microcystin-LR (MC-LR) is the most abundant and toxic microcystin congener and has been classified as a potential human carcinogen (Group 2B) by the International Agency for Research on Cancer. However, the mechanisms underlying the genotoxic effects of MC-LR during chronic exposure are still poorly understood. In the present study, human–hamster hybrid (A_L) cells were exposed to MC-LR for varying lengths of time to investigate the role of nitrogen radicals in MC-LR-induced genotoxicity. The mutagenic potential at the CD59 locus was more than 2-fold higher (p < 0.01) in A_L cells exposed to a cytotoxic concentration (1 μmol/L) of MC-LR for 30 days than in untreated control cells, which was consistent with the formation of micronucleus. MC-LR caused a dose-dependent increase in nitric oxide (NO) production in treated cells. Moreover, this was blocked by concurrent treatment with the NO synthase inhibitor N^G-methyl-l-arginine (l-NMMA), which suppressed MC-LR-induced mutations as well. The survival of mitochondrial DNA-depleted (ρ⁰) A_L cells was markedly decreased by MC-LR treatment compared to that in A_L cells, while the CD59 mutant fraction was unaltered. These results provided clear evidence that the genotoxicity associated with chronic MC-LR exposure in mammalian cells was mediated by NO and might be considered as a basis for the development of therapeutics that prevent carcinogenesis.     

Bioassay: A useful tool for evaluating reclaimed water safety

Wastewater reclamation and reuse has been proved to be an effective way to relieve the fresh water crisis. However, toxic contaminants remaining in reclaimed water could lead to potential risk for reuse, and the conventional water quality standards have difficulty guaranteeing the safety of reclaimed water. Bioassays can vividly reflect the integrated biological effects of multiple toxic substances in water as a whole, and could be a powerful tool for evaluating the safety of reclaimed water. Therefore, in this study, the advantages and disadvantages of using bioassays for evaluating the safety of reclaimed water were compared with those of conventional water quality standards. Although bioassays have been widely used to describe the toxic effects of reclaimed water and treatment efficiency of reclamation techniques, a single bioassay cannot reflect the complex toxicity of reclaimed water, and a battery of bioassays involving multiple biological effects or in vitro tests with specific toxicity mechanisms would be recommended. Furthermore, in order to evaluate the safety of reclaimed water based on bioassay results, various methods including potential toxicology, the toxicity unit classification system, and a potential eco-toxic effects probe are summarized as well. Especially, some integrated ranking methods based on a bioassay battery involving multiple toxicity effects are recommended as useful tools for evaluating the safety of reclaimed water, which will benefit the promotion and guarantee the rapid development of the reclamation and reuse of wastewater.     

全氟辛酸对大肠杆菌的氧化胁迫和膜损伤

全氟辛酸(perfluorooctanoic acid,PFOA)因其具有极高的化学稳定性和良好的疏水疏油性而在工业生产中广泛使用,但近年来被认为是一种在环境中广泛分布的持久性有机污染物.利用流式细胞术等检测技术,研究了PFOA对大肠杆菌(Escherichia coli,E.coli)的氧化胁迫和膜损伤,并对其毒性作用机制进行了初步的探索.结果表明,在PFOA胁迫下,大肠杆菌胞内活性氧(reactive oxygen species,ROS)含量增加,膜脂肪酸不饱和度降低,丙二醛(malondialdehyde,MDA)浓度升高、细胞膜通透性增大、跨膜电位降低,而细胞膜上的Na+K+-ATPase、Ca2+Mg2+-ATPase活性随时间的延长代偿性地先上升后降低.由此说明,在PFOA胁迫下,大肠杆菌细胞内升高的ROS与细胞膜不饱和脂肪酸发生过氧化反应,降低膜脂肪酸的饱和度,使得MDA在细胞内积累,进一步引起细胞膜损伤及其上相关ATPase活性降低,最终导致大肠杆菌细胞失活或死亡.实验结果对研究PFOA胁迫下环境生态毒理提供更多依据.     

Molecular toxicity and defense mechanisms induced by silver nanoparticles in Drosophila melanogaster

The widely use of silver nanoparticles (AgNPs) as antimicrobial agents gives rise to potential environmental risks. AgNPs exposure have been reported to cause toxicity in animals. Nevertheless, the known mechanisms of AgNPs toxicity are still limited. In this study, we systematically investigated the toxicity of AgNPs exposure using Drosophila melanogaster. We show here that AgNPs significantly decreased Drosophila fecundity, the third-instar larvae weight and rates of pupation and eclosion in a dose-dependent manner. AgNPs reduced fat body cell viability in MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays. AgNPs caused DNA damage in hemocytes and S2 cells. Interestingly, the mRNA levels of the entire metallothionein gene family were increased under AgNPs exposure as determined by RNA-seq analysis and validated by qRT-PCR, indicating that Drosophila responded to the metal toxicity of AgNPs by producing metallothioneins for detoxification. These findings provide a better understanding of the mechanisms of AgNPs toxicity and may provide clues to effect on other organisms, including humans.     

双酚A诱导人乳腺癌MCF-7细胞上皮间质化的研究

双酚A(BPA)是一类典型的环境雌激素,能干扰机体正常内分泌系统.作为一种激素相关疾病,乳腺癌的发生发展与BPA暴露的关系已引起人们的关注.本研究旨在探讨BPA对人乳腺癌MCF-7细胞上皮细胞间质化(EMT)的诱导作用.经BPA处理的MCF-7细胞,采用MTT试验检测BPA对细胞活力的影响,Transwell试验检测BPA对细胞迁移能力的影响,Real-time RT-PCR、Western Blot检测BPA对上皮型蛋白标志物E-cadherin、间质型蛋白标志物Vimentin及EMT相关转录因子Snail表达的影响.结果发现,低浓度BPA能够促进MCF-7细胞的增殖,显著增强细胞的迁移能力.BPA处理能抑制E-cadherin的表达,促进Vimentin及Snail的表达.研究结果提示,BPA处理可能通过促进Snail的表达而调控EMT相关蛋白标志物的表达,进而增强乳腺癌MCF-7细胞的迁移能力.     

草酸促进双酚A在黏土矿物悬浮液中光降解研究

选择两种常见的天然黏土矿物高岭石和蒙脱石,研究了有机污染物双酚A(BPA)在其表面的吸附及草酸对黏土矿物悬浮液中BPA光降解的影响.结果表明,BPA在两种黏土矿物表面的吸附量较小,吸附符合Langmuir等温式.在250W金属卤化物灯(λ≥360nm)照射下,草酸可显著促进BPA在高岭石和蒙脱石悬浮液中的光降解,降解动力学符合Langmuir-Hinshelwood方程. 降解速率受pH值的影响较大,pH=4.0时速度最快,光降解速率同时受草酸浓度的影响.最后,通过分析矿物中铁的化学环境及反应过程中铁浓度变化,分析了草酸促进BPA在黏土矿物悬浮液中光降解的可能机制.