致癌机制的当前认识：遗传毒物与非遗传毒物

致癌机制的当前认识：遗传毒物与非遗传毒物印木泉上海第二军医大学卫生毒理学教研室２００４３３自Ａｍｅｓ发表“致癌物和致突物”一文后不久，他建立了用诱导的大鼠肝微粒体组份掺入的致突变试验，以此证实肿瘤是由突变引起的细胞复制的疾病。这种评价接触致癌物危险度...

基于毒性效应的非目标化学品鉴别技术进展

现代社会大量化学品的生产与广泛使用造成了地表水、地下水、沉积物、土壤等环境受到污染,并对人体健康和生态系统构成威胁。基于毒性效应的关键致毒物质鉴别技术(effect directed analysis,EDA)已经在水体、沉积物的致毒物筛选方面得到了一定的应用。但是由于污染物组成复杂、范围广、基质干扰高、同分异构体广泛存在、人工合成标样缺少等问题,非目标致毒化合物的鉴别成为了EDA的瓶颈技术。逐渐发展的色谱与质谱技术、数据库指标在化合物筛选识别中发挥了重要作用。本文综述了基于高分辨质谱,数据库搜索,色谱保留特征,模型构建来筛选识别化合物的方法,总结了近年来化合物筛选识别方法在环境新型污染物及药物筛选等方面的应用并分析了化合物筛选识别所存在的问题与应用前景。这些方法可以提高非目标化合物筛选的准确性和通量,减少样品复杂性和基质干扰带来的负面影响,从而有利于未知化合物的确定。

关于生态毒理学与环境毒理学几个基本概念的见解

对生态毒理学和环境毒理学的几个基本概念进行了论述.首先,论述生态毒理学和环境毒理学的定义和各自的研究范畴,提出二者区分的条件和方法;其次,对“毒物”和“非毒物”的概念进行论述,否定了“物质即毒物”的论点;第三,论述“靶器官”概念的局限性及其对学科发展的不利影响,提出以“敏感器官”概念代替“靶器官”的见解.

Expression and function of renal and hepatic organic anion transporters in extrahepatic cholestasis

Obstructive jaundice occurs in patients suffering from cholelithiasis and from neoplasms affecting the pancreas and the common bile duct.The absorption,distribution and elimination of drugs are impaired during this pathology.Prolonged cholestasis may alter both liver and kidney function.Lactam antibiotics,diuretics,non-steroidal anti-inflammatory drugs,several antiviral drugs as well as endogenous compounds are classified as organic anions.The hepatic and renal organic anion transport pathways play a key role in the pharmacokinetics of these compounds.It has been demonstrated that acute extrahepatic cholestasis is associated with increased renal elimination of organic anions.The present work describes the molecular mechanisms involved in the regulation of the expression and function of the renal and hepatic organic anion transporters in extrahepatic cholestasis,such as multidrug resistanceassociated protein 2,organic anion transporting polypeptide 1,organic anion transporter 3,bilitranslocase,bromosulfophthalein/bilirubin binding protein,organic anion transporter 1 and sodium dependent bile salt transporter.The modulation in the expression of renal organic anion transporters constitutes a compensatory mechanism to overcome the hepatic dysfunction in the elimination of organic anions.

Protein and non-protein sulfhydryls and disulfides in gastric mucosa and liver after gastrotoxic chemicals and sucralfate: Possible new targets of pharmacologic agents

AIM： To investigate the role of major non-protein and protein sulfhydryls and disulfides in chemically induced gastric hemorrhagic mucosal lesions （HML） and the mechanism of gastroprotective effect of sucralfate.METHODS： Rats were given 1 mL of 75% ethanol, 25%NaCl, 0.6 mol/L HCI, 0.2 mol/L NaOH or 1% ammonia solutions intragastrically （i.g.） and sacrificed 1, 3, 6 or 12 min later. Total （reduced and oxidized） glutathione （GSH ＋ GSSG）, glutathione disulfide （GSSG）, protein free sulfhydryls （PSH）, protein-glutathione mixed disulfides （PSSG） and protein cystine disulfides （PSSP） were measured in gastric mucosa and liver.RESULTS： Reduced glutathione （GSH） was depleted in the gastric mucosa after ethanol, HCI or NaCl exposure,while oxidized glutathione （GSSG） concentrations increased, except by HCI and NaOH exposure. Decreased levels of PSH after exposure to ethanol were observed,NaCl or NaOH while the total protein disulfides were increased. Ratios of reduced to oxidized glutathione or sulfhydrils to disulfides were decreased by all chemicals.No changes in thiol homeostasis were detected in the liver after i.g. abbreviation should be spelled out the first time here administration of ethanol. Sucralfate increased the concentrations of GSH and PSH and prevented the ethanol-induced changes in gastric mucosal thiol concentrations.CONCLUSION： Our modified methods are now suitable for direct measurements of major protein and nonprotein thiols/disulfides in the gastric mucosa or liver.A common element in the pathogenesis of chemically induced HML and in the mechanism of gastroprotective drugs seems to be the decreased ratios of reduced and oxidized glutathione as well as protein sulfhydryls and disulfides.

An extract from the earthworm Eisenia fetida non-specifically inhibits the activity of influenza and adenoviruses

OBJECTIVE： To test the in vitro antiviral activity of a crude tissue extract （CTE/from the earthworm Eisenia fetida, determine any effective components in the CTE, andelucidate possiblemechanismsofaction. METHODS： A CTE was made by homogenizing earthworms, followed by treatment with ammoni- um sulfate, then thermal denaturation. Inhibition of virus-induced cytopathic effect （CPE） was used to assess antiviral activity. Chromatographic analy- sis was used to identify effective components in the CTE. RESULTS： The CTE inhibited viral CPE at non-cyto- toxic concentrations. Chromatography indicated that antiviral components corresponded to three active peaks indicative of proteases, nucleases and lysozymes. For adenoviruses, reduction in viral ac- tivity occurred for 100 lag/mL CTE. The reduction in adenoviral activity for four fractions was 100%, 91.8%, 86.9%, and 94.7%. For influenza viruses, re- duction in viral activity of 100%, 86.6%, 69.1% and 88.3% was observed for 37 pg/mL CTE. In addition, three active fractions mixture had stronger antiviral activity （98.7% and 96.7%） than three fractions alone.Gel electrophoresis results indicated that nu- cleases from E. fetida could degrade the genome of influenza viruses and adenoviruses. CONCLUSION： The earthworm CTE displayed non-specific antiviral properties, possibly mediated by a combination of proteases, nucleases and lyso- zymes. Nucleases likely participate in the antiviral process, and degrade the genome of the virus thereby preventing further replication.

Impacts of climate change on the ecotoxicology of chemical contaminants in estuarine organisms

Global climate change effects will vary geographically, and effects on estuaries should be independently considered. This review of the impacts of climate change on the ecotoxicology of chemical contaminants aims to summarize responses that are specific to estuafine species. Estuarine organisms are uniquely adapted to large fluctuations in temperature, salinity, oxygen, and pH, and yet future changes in climate may make them more susceptible to chemical contaminants. Recent research has hig- hlighted the interactive effects of chemical and nonchemical stressors on chemical uptake, metabolism, and organism survival. Assessments have revealed that the nature of the interaction between climate variables and chemical pollution will depend on es- tuarine species and life stage, duration and timing of exposure, prior stressor exposure, and contaminant class. A need for further research to elucidate mechanisms of toxicity under different abiotic conditions and to incorporate climate change factors into toxicity testing was identified. These efforts will improve environmental risk assessment of chemical contaminants and manage- ment capabilities under changing climate conditions [Current Zoology 61 （4）： 641-652, 2015].

Virus-induced gene silencing and its application in plant functional genomics

Virus-induced gene silencing is regarded as a powerful and efficient tool for the analysis of gene function in plants because it is simple, rapid and transformation-free. It has been used to perform both forward and reverse genetics to identify plant functional genes. Many viruses have been developed into virus-induced gene silencing vectors and gene functions involved in development, biotic and abiotic stresses, metabolism, and cellular signaling have been reported. In this review, we discuss the development and application of virus-induced gene silencing in plant functional genomics.

Tailoring non-viral delivery vehicles for transporting genome-editing tools

The CRISPR-Cas system, especially the type II CRISPR-Cas9 system from Streptococcuspyogenes, has rapidly emerged as a popular genome editing tool. The development of Cas9 derivatives further expanded the toolbox of CRISPR- Cas9 based genome editing kit. However, therapeutic transla- tion of the CRISPR-Cas9 system in vivo is severely impeded by the absence of an appropriate delivery carrier. The complex- ity and high molecular weight of the CRISPR-Cas9 system, together with the physiological barriers for nucleus targeted cargo transportation have made it a huge challenge for in vivo therapeutic CRISPR-Cas9 delivery. Currently, the main stream carriers for systemic delivery of CRISPR-Cas9 are vi- ral based, such as adeno-associated virus. However, the safety concerns surrounding viral vectors call for the development of non-viral nanocarriers. In this review, we survey the recent advances in the development of non-viral delivery systems for CRISPR-Cas9. Challenges and future directions in this field are also discussed.