Applied In Vitro Toxicology最新文献_第9页

Review: Endogenously Produced Volatiles for In Vitro Toxicity Testing Using Cell Lines. 回顾：利用细胞株进行体外毒性测试的内源性挥发性物质

Applied In Vitro Toxicology Pub Date : 2018-06-01 DOI: 10.1089/aivt.2017.0038

Brett R Winters, Joachim D Pleil, Jayne C Boyer, Leena A Nylander-French, M Ariel Geer Wallace, Michael C Madden

引用次数: 0

Air-Liquid Interface In Vitro Models for Respiratory Toxicology Research: Consensus Workshop and Recommendations. 呼吸毒理学研究的体外气液界面模型:共识研讨会和建议。

Applied In Vitro Toxicology Pub Date : 2018-06-01 DOI: 10.1089/aivt.2017.0034

Ghislaine Lacroix, Wolfgang Koch, Detlef Ritter, Arno C Gutleb, Søren Thor Larsen, Thomas Loret, Filippo Zanetti, Samuel Constant, Savvina Chortarea, Barbara Rothen-Rutishauser, Pieter S Hiemstra, Emeric Frejafon, Philippe Hubert, Laura Gribaldo, Peter Kearns, Jean-Marc Aublant, Silvia Diabaté, Carsten Weiss, Antoinette de Groot, Ingeborg Kooter

{"title":"Air-Liquid Interface In Vitro Models for Respiratory Toxicology Research: Consensus Workshop and Recommendations.","authors":"Ghislaine Lacroix, Wolfgang Koch, Detlef Ritter, Arno C Gutleb, Søren Thor Larsen, Thomas Loret, Filippo Zanetti, Samuel Constant, Savvina Chortarea, Barbara Rothen-Rutishauser, Pieter S Hiemstra, Emeric Frejafon, Philippe Hubert, Laura Gribaldo, Peter Kearns, Jean-Marc Aublant, Silvia Diabaté, Carsten Weiss, Antoinette de Groot, Ingeborg Kooter","doi":"10.1089/aivt.2017.0034","DOIUrl":"https://doi.org/10.1089/aivt.2017.0034","url":null,"abstract":"In vitro air-liquid interface (ALI) cell culture models can potentially be used to assess inhalation toxicology endpoints and are usually considered, in terms of relevancy, between classic (i.e., submerged) in vitro models and animal-based models. In some situations that need to be clearly defined, ALI methods may represent a complement or an alternative option to in vivo experimentations or classic in vitro methods. However, it is clear that many different approaches exist and that only very limited validation studies have been carried out to date. This means comparison of data from different methods is difficult and available methods are currently not suitable for use in regulatory assessments. This is despite inhalation toxicology being a priority area for many governmental organizations. In this setting, a 1-day workshop on ALI in vitro models for respiratory toxicology research was organized in Paris in March 2016 to assess the situation and to discuss what might be possible in terms of validation studies. The workshop was attended by major parties in Europe and brought together more than 60 representatives from various academic, commercial, and regulatory organizations. Following plenary, oral, and poster presentations, an expert panel was convened to lead a discussion on possible approaches to validation studies for ALI inhalation models. A series of recommendations were made and the outcomes of the workshop are reported.","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":"4 2","pages":"91-106"},"PeriodicalIF":0.0,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/aivt.2017.0034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38400950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 119

Through the Looking Glass: In Vitro Models for Inhalation Toxicology and Interindividual Variability in the Airway. 透过镜子：吸入毒理学和气道个体间变异的体外模型。

Applied In Vitro Toxicology Pub Date : 2018-06-01 DOI: 10.1089/AIVT.2018.0002

Samantha C. Faber, S. McCullough

{"title":"Through the Looking Glass: In Vitro Models for Inhalation Toxicology and Interindividual Variability in the Airway.","authors":"Samantha C. Faber, S. McCullough","doi":"10.1089/AIVT.2018.0002","DOIUrl":"https://doi.org/10.1089/AIVT.2018.0002","url":null,"abstract":"With 7 million deaths reported annually from air pollution alone, it is evident that adverse effects of inhaled toxicant exposures remain a major public health concern in the 21st century. Assessment and characterization of the impacts of air pollutants on human health stems from epidemiological and clinical studies, which have linked both outdoor and indoor air contaminant exposure to adverse pulmonary and cardiovascular health outcomes. Studies in animal models support epidemiological findings and have been critical in identifying systemic effects of environmental chemicals on cognitive abilities, liver disease, and metabolic dysfunction following inhalation exposure. Likewise, traditional monoculture systems have aided in identifying biomarkers of susceptibility to inhaled toxicants and served as a screening platform for safety assessment of pulmonary toxicants. Despite their contributions, in vivo and classic in vitro models have not been able to accurately represent the heterogeneity of the human population and account for interindividual variability in response to inhaled toxicants and susceptibility to the adverse health effects. Development of new technologies that can investigate genetic predisposition, are cost and time efficient, and are ethically sound, will enhance elucidation of mechanisms of inhalation toxicity, and aid in the development of novel pharmaceuticals and/or safety evaluation. This review will describe the classic and novel cell-based inhalation toxicity models and how these emerging technologies can be incorporated into regulatory or nonregulatory testing to address interindividual variability and improve overall human health.","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":"4 2 1","pages":"115-128"},"PeriodicalIF":0.0,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/AIVT.2018.0002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48455906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 28

Nonanimal Approaches to Assessing the Toxicity of Inhaled Substances: Current Progress and Future Promise 评估吸入物质毒性的非动物方法：当前进展和未来前景

Applied In Vitro Toxicology Pub Date : 2018-06-01 DOI: 10.1089/AIVT.2018.29015.RTL

A. Clippinger, D. Allen, H. Behrsing, P. Hinderliter, R. Landsiedel, Emily N. Reinke, V. Stone

引用次数: 4

Transcriptomic, Proteomic, and Functional Long-Term Characterization of Multicellular Three-Dimensional Human Liver Microtissues. 多细胞三维人类肝脏微组织的转录组学、蛋白质组学和功能长期表征。

Applied In Vitro Toxicology Pub Date : 2018-03-01 DOI: 10.1089/aivt.2017.0022

Simon Messner, Lisa Fredriksson, Volker M Lauschke, Katrin Roessger, Claudia Escher, Magdalena Bober, Jens M Kelm, Magnus Ingelman-Sundberg, Wolfgang Moritz

{"title":"Transcriptomic, Proteomic, and Functional Long-Term Characterization of Multicellular Three-Dimensional Human Liver Microtissues.","authors":"Simon Messner, Lisa Fredriksson, Volker M Lauschke, Katrin Roessger, Claudia Escher, Magdalena Bober, Jens M Kelm, Magnus Ingelman-Sundberg, Wolfgang Moritz","doi":"10.1089/aivt.2017.0022","DOIUrl":"10.1089/aivt.2017.0022","url":null,"abstract":"Three-Dimensional (3D) liver microtissues, specifically prepared from primary human hepatocytes (PHH) in coculture with nonparenchymal cells (NPCs), have been shown to be a valuable tool for in vitro toxicology. However, a lack of thorough characterization on a functional, transcriptomic, and proteomic level of such models during long-term cultivation is evident. By integrating multiple omics technologies, we provide in this study an in-depth long-term characterization of 3D microtissues composed of PHH from three different donors cocultured with primary NPCs. The 3D human liver microtissues (hLiMTs) exhibited stable adenosine triphosphate (ATP) content and albumin secretion over 5 weeks. Histological analysis indicated a healthy liver tissue with polarized expression of bile salt export pump (BSEP) and multidrug resistance protein 2 (MRP2) in a structure reminiscent of bile canaliculi. The 3D microtissues exhibited stable basal and inducible cytochrome P450 activities up to 5 weeks in culture. Analysis of 40,716 transcripts using RNA arrays revealed distinct similarities to native human liver gene expression. Long-term culture showed a stable phenotype up to 5 weeks, with differences in liver gene expression primarily attributed to individual donors. Proteomic profiling of 2200 unique proteins by label-free LC-MS/MS revealed a relatively stable protein expression where only 7.3% were up- or downregulated more than twofold from day 7 to 35 in culture. Taken together, these results suggest that hLiMTs represent a responsive and physiologically relevant in vitro liver model that maintains stable function over 5 weeks and is therefore well suited for repeated-dose toxicity testing.","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":"4 1","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"2018-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38400949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metabolism of Diazinon in Rainbow Trout Liver Slices. 虹鳟肝片中二嗪农的代谢。

Applied In Vitro Toxicology Pub Date : 2018-03-01 DOI: 10.1089/aivt.2017.0025

Mark A Tapper, Jose A Serrano, Patricia K Schmieder, Dean E Hammermeister, Richard C Kolanczyk

{"title":"Metabolism of Diazinon in Rainbow Trout Liver Slices.","authors":"Mark A Tapper, Jose A Serrano, Patricia K Schmieder, Dean E Hammermeister, Richard C Kolanczyk","doi":"10.1089/aivt.2017.0025","DOIUrl":"https://doi.org/10.1089/aivt.2017.0025","url":null,"abstract":"Introduction: Understanding biotransformation pathways in aquatic species is an integral part of ecological risk assessment with respect to the potential bioactivation of chemicals to more toxic metabolites. The long-range goal is to gain sufficient understanding of fish metabolic transformation reactions to be able to accurately predict fish xenobiotic metabolism. While some metabolism data exist, there are few fish in vivo exposure studies where metabolites have been identified and the metabolic pathways proposed. Previous biotransformation work has focused on in vitro studies which have the advantage of high throughput but may have limited metabolic capabilities, and in vivo studies which have full metabolic capacity but are low throughput. An aquatic model system with full metabolic capacity in which a large number of chemicals could be tested would be a valuable tool.Materials and methods: The current study evaluated the ex vivo rainbow trout liver slice model, which has the advantages of high throughput as found in vitro models and non-dedifferentiated cells and cell to cell communication found in in vivo systems. The pesticide diazinon, which has been previously tested both in vitro and in vivo in a number of mammalian and aquatic species including rainbow trout, was used to evaluate the ex vivo slice model as a tool to study biotransformation pathways.Results/discussion: While somewhat limited by the analytical chemistry method employed, results of the liver slice model, mainly that hydroxypyrimidine was the major diazinon metabolite, are in line with the results of previous rainbow trout in vivo studies.Conclusion: Therefore, the rainbow trout liver slice model is a useful tool for the study of metabolism in aquatic species.","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":"4 1","pages":"13-23"},"PeriodicalIF":0.0,"publicationDate":"2018-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/aivt.2017.0025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37128433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10

Estrogen Mitigates the Negative Effects of Arsenic Contamination in an In Vitro Wound Model. 雌激素在体外创伤模型中减轻砷污染的负面影响。

Applied In Vitro Toxicology Pub Date : 2018-03-01 DOI: 10.1089/aivt.2017.0020

Bronson I Pinto, Oscar R Lujan, Stephan A Ramos, Catherine R Propper, Robert S Kellar

{"title":"Estrogen Mitigates the Negative Effects of Arsenic Contamination in an In Vitro Wound Model.","authors":"Bronson I Pinto, Oscar R Lujan, Stephan A Ramos, Catherine R Propper, Robert S Kellar","doi":"10.1089/aivt.2017.0020","DOIUrl":"10.1089/aivt.2017.0020","url":null,"abstract":"Arsenic, a naturally occurring environmental contaminant, is harmful to humans at elevated concentrations. Increased levels of arsenic in the environment occur as a result of human activities and from natural geologically sourced leaching into ground and surface water. These sources pose an exposure risk above the USEPA standard to individuals whose food and water sources become contaminated. Arsenic exposure negatively impacts organ function and increases the risk for developing pathologies, including cancer. Some of the effects of arsenic on cancer translate to normal cell function in wound healing. To evaluate whether arsenic influences wound healing, an in vitro scratch assay was employed to study the effects of arsenic on cellular migration, which is a key component in the normal wound-healing process. In this study, skin cells were exposed to environmentally relevant concentrations of arsenic, and wound closure was evaluated. Results indicated that arsenic significantly decreased the rate of cellular migration in the scratch assay when compared with controls. In addition, estradiol, which has been shown to positively influence cellular and tissue processes involved in wound healing, reversed the slowing effects of arsenic on wound closure. These results suggest that arsenic contamination may inhibit, and estrogen may provide a therapeutic benefit for individuals with arsenic-contaminated wounds.","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":"4 1","pages":"24-29"},"PeriodicalIF":0.0,"publicationDate":"2018-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/aivt.2017.0020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37128434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Measurement of kinetic parameters for biotransformation of polycyclic aromatic hydrocarbons by trout liver S9 fractions: Implications for bioaccumulation assessment. 鳟鱼肝脏S9馏分生物转化多环芳烃动力学参数的测定:对生物积累评价的意义。

Applied In Vitro Toxicology Pub Date : 2018-01-01 DOI: 10.1089/aivt.2017.0005

John W Nichols, Melanie A Ladd, Patrick N Fitzsimmons

{"title":"Measurement of kinetic parameters for biotransformation of polycyclic aromatic hydrocarbons by trout liver S9 fractions: Implications for bioaccumulation assessment.","authors":"John W Nichols, Melanie A Ladd, Patrick N Fitzsimmons","doi":"10.1089/aivt.2017.0005","DOIUrl":"https://doi.org/10.1089/aivt.2017.0005","url":null,"abstract":"In vitro substrate depletion methods developed by the pharmaceutical industry are being used with increasing frequency to support chemical bioaccumulation assessments for fish. However, the application of these methods to high log K ow chemicals poses special challenges. Biotransformation of three polycyclic aromatic hydrocarbons (PAHs) was measured using trout liver S9 fractions. Measured activity declined with incubation time and was reduced by acetone (used as a spiking solvent) at concentrations greater than 0.5%. Addition of alamethicin, a pore-forming peptide used to support UDP-glucuronosyltransferase activity, also reduced activity in a concentration-dependent manner. The substrate concentration dependence of activity was evaluated to estimate K M and V max values for each compound. Derived kinetic constants suggested that all three PAHs are transformed by the same reaction pathway and indicated an inverse correlation between K M and chemical log K ow. Binding effects on activity were evaluated by measuring unbound chemical concentrations across a range of S9 protein levels. Reaction rates were proportional to the unbound concentration except when these concentrations approached saturating levels, providing a direct demonstration of the free chemical hypothesis. These findings suggest that previous in vitro work with high log K ow compounds was conducted at inappropriately high substrate concentrations resulting in underestimation of true in vivo activity. Preliminary calculations also indicate that PAH metabolism in fish may approach saturation during standardized in vivo testing efforts, potentially resulting in concentration-dependent accumulation and/or steady-state levels of accumulation greater than those which occur in a natural setting.","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":" ","pages":"365-378"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/aivt.2017.0005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40451461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 25

Creating a Structured AOP Knowledgebase via Ontology-Based Annotations. 通过基于本体的注解创建结构化的AOP知识库。

Applied In Vitro Toxicology Pub Date : 2017-12-01 DOI: 10.1089/aivt.2017.0017

Cataia Ives, Ivana Campia, Rong-Lin Wang, Clemens Wittwehr, Stephen Edwards

{"title":"Creating a Structured AOP Knowledgebase via Ontology-Based Annotations.","authors":"Cataia Ives, Ivana Campia, Rong-Lin Wang, Clemens Wittwehr, Stephen Edwards","doi":"10.1089/aivt.2017.0017","DOIUrl":"https://doi.org/10.1089/aivt.2017.0017","url":null,"abstract":"Introduction: The Adverse Outcome Pathway framework is increasingly used to integrate data generated based on traditional and emerging toxicity testing paradigms. As the number of AOP descriptions has increased, so has the need to define the AOP in computable terms.Materials and methods: Herein, we present a comprehensive annotation of 172 AOPs housed in the AOP-Wiki as of December 4, 2016 using terms from existing biological ontologies.Results: AOP Key Events (KEs) were assigned ontology terms using a concept called the Event Component, which consists of a Process, an Object, and an Action term, with each term originating from ontologies and other controlled vocabularies. Annotation of KEs with ontology classes from fourteen ontologies and controlled vocabularies resulted in a total of 685 KEs being annotated with a total of 809 Event Components. A set of seven conventions resulted, defining the annotation of KEs via Event Components.Discussion: This expanded annotation of AOPs allows computational reasoners to aid in both AOP development and applications. In addition, the incorporation of explicit biological objects will reduce the time required for converting a qualitative AOP description into a conceptual model that can support computational modeling. As high throughput genomics becomes a more important part of the high throughput toxicity testing landscape, the new approaches described here for annotating key events will also promote the visualization and analysis of genomics data in an AOP context.","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":"3 4","pages":"298-311"},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/aivt.2017.0017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36352038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 48

An Update on Adverse Outcome Pathways Leading to Liver Injury. 导致肝损伤的不良结果通路的最新进展。

Applied In Vitro Toxicology Pub Date : 2017-12-01 Epub Date: 2017-12-06 DOI: 10.1089/aivt.2017.0027

Eva Gijbels, Mathieu Vinken

引用次数: 15