General, Applied and Systems Toxicology最新文献_第5页

Mitochondria‐Specific Mouse Gene Array and its Application in Toxicogenomics 线粒体特异性小鼠基因阵列及其在毒物基因组学中的应用

General, Applied and Systems Toxicology Pub Date : 2011-09-15 DOI: 10.1002/9780470744307.GAT209

V. Desai

{"title":"Mitochondria‐Specific Mouse Gene Array and its Application in Toxicogenomics","authors":"V. Desai","doi":"10.1002/9780470744307.GAT209","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT209","url":null,"abstract":"In recent years, mitochondria have gained significant attention in toxicology because of their involvement in several drug-induced toxicities and in the pathogenesis of a number of degenerative diseases. Thus far, numerous molecular and biochemical assays have been developed and utilized to understand the association between mitochondria and drug toxicities or disease processes. However, the knowledge gained by these assays is inadequate to obtain a comprehensive outlook of the mitochondrial activity during toxic exposures and the underlying pathologies. High-throughput technologies, such as DNA microarray, have great potential in advancing genomic research in toxicology. This technology allows expression profiling of thousands of genes in a single experiment. Building on this technology, a mitochondria-specific mouse oligonucleotide microarray (MitoChip) was developed, which is described in this review. This review also discusses results generated using the MitoChip in studies that were designed to elucidate the molecular mechanisms of altered mitochondrial function induced by anti-HIV drugs (zidovudine and lamivudine) and a weight-loss dietary supplement (usnic acid) in mice. The results from these studies clearly demonstrate that the MitoChip is a valuable genomic tool and can help unravel the underlying molecular basis of impaired mitochondrial function in drug-induced toxicities. \u0000 \u0000 \u0000Keywords: \u0000 \u0000anti-HIV drugs; \u0000gene expression profiles; \u0000mitochondria; \u0000MitoChip; \u0000mouse; \u0000usnic acid","PeriodicalId":325382,"journal":{"name":"General, Applied and Systems Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117135431","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: 0

Next-Generation Sequencing: A Revolutionary Tool for Toxicogenomics 新一代测序:毒物基因组学的革命性工具

General, Applied and Systems Toxicology Pub Date : 2011-09-15 DOI: 10.1002/9780470744307.GAT232

Z. Su, B. Ning, H. Fang, H. Hong, R. Perkins, W. Tong, Leming Shi

{"title":"Next-Generation Sequencing: A Revolutionary Tool for Toxicogenomics","authors":"Z. Su, B. Ning, H. Fang, H. Hong, R. Perkins, W. Tong, Leming Shi","doi":"10.1002/9780470744307.GAT232","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT232","url":null,"abstract":"Over the past five years, DNA sequencing has been undergoing fundamental changes due to the rapid development of next-generation sequencing (NGS) technologies. NGS technologies have been offering unprecedented opportunities for high-throughput functional genomic research, and opening up new fields and novel applications in biology, life sciences, and biomedicine. The major advantages of NGS technologies over conventional Sanger sequencing include sequencing cost reduction from about 0.50 per kilobase to as little as 0.001 per kilobase, and massive parallelism that dramatically increases sequencing throughput. However, Sanger-based approaches provide advantages in terms of read-length and base call accuracy. \u0000 \u0000 \u0000 \u0000In this chapter, we first describe the fundamental principles of four currently commercialized NGS platforms from Roche/454, Illumina, Life Technologies, and Helicos BioSciences. Next we discuss the challenges in analyzing short reads from NGS, and outline major applications of these new technologies. Finally, we compare data between NGS and microarrays with a toxicogenomics study aiming at gene expression profiling. \u0000 \u0000 \u0000Keywords: \u0000 \u0000next-generation sequencing (NGS); \u0000ultra high-throughput sequencing; \u0000RNA-Seq; \u0000ChIP-Seq; \u0000transcriptome; \u0000toxicogenomics; \u0000sequence alignment","PeriodicalId":325382,"journal":{"name":"General, Applied and Systems Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117181588","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: 6

Biomarkers of System Response to Therapeutic Intervention 系统对治疗干预反应的生物标志物

General, Applied and Systems Toxicology Pub Date : 2011-09-15 DOI: 10.1002/9780470744307.GAT238

Ludmila V. Danilova, M. Ochs

引用次数: 0

Use of Proteomic and Metabolomic Techniques in Ecotoxicological Research 蛋白质组学和代谢组学技术在生态毒理学研究中的应用

General, Applied and Systems Toxicology Pub Date : 2011-09-15 DOI: 10.1002/9780470744307.GAT215

M. Sepúlveda, K. Ralston-Hooper, Brian C. Sanchez, Amber Hopf-jannasch, S. D. Baker, N. Diaz, J. Adamec

{"title":"Use of Proteomic and Metabolomic Techniques in Ecotoxicological Research","authors":"M. Sepúlveda, K. Ralston-Hooper, Brian C. Sanchez, Amber Hopf-jannasch, S. D. Baker, N. Diaz, J. Adamec","doi":"10.1002/9780470744307.GAT215","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT215","url":null,"abstract":"Over the last decade, the environmental sciences have witnessed an incredible movement towards the utilization of high through-put molecular tools that are capable of detecting simultaneous changes of hundreds and even thousands of molecules and molecular components after exposure of organisms to different environmental stressors. These techniques have received lots of attention because they not only offer the potential to unravel novel mechanisms of physiological and toxic action, but they also are amenable for the discovery of biomarkers of exposure and effects. In this chapter we will review the state of knowledge of two of these holistic tools in ecotoxicological research: Proteomics and metabolomics. We will follow this review with a presentation of three of our own case studies utilizing proteomic and metabolomic tools: (i) Analysis of proteomic responses in fish exposed to different types of contaminants using GeneGo™; (ii) Comparison of proteomic and metabolomic responses in aquatic invertebrates exposed to herbicides; and (ii) Use of metabolomics to characterize egg quality in fish eating birds exposed to persistent organic pollutants. We will end with some ideas for future studies and research needs. \u0000 \u0000 \u0000Keywords: \u0000 \u0000proteomics; \u0000metabolomics; \u0000ecotoxicology; \u0000fish; \u0000invertebrates; \u0000birds; \u0000aquatic; \u0000wildlife; \u0000biomarkers; \u0000contaminants; \u0000toxicity; \u0000pollution","PeriodicalId":325382,"journal":{"name":"General, Applied and Systems Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132020826","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: 3

Application of Metabonomic Approach in Target Organ Toxicity 代谢组学方法在靶器官毒性中的应用

General, Applied and Systems Toxicology Pub Date : 2011-09-15 DOI: 10.1002/9780470744307.GAT220

Athina Zira, S. Theocharis

引用次数: 1

Implementing Systems Toxicology in Drug Development for Regulatory Decision Making 在药物开发中实施系统毒理学以进行监管决策

General, Applied and Systems Toxicology Pub Date : 2011-09-15 DOI: 10.1002/9780470744307.GAT248

J. Sina, F. Sistare

{"title":"Implementing Systems Toxicology in Drug Development for Regulatory Decision Making","authors":"J. Sina, F. Sistare","doi":"10.1002/9780470744307.GAT248","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT248","url":null,"abstract":"The concept of integrating molecular and biochemical data from new technologies with more traditional endpoints to develop a more complete understanding of risks and benefits in drug development has gained wide acceptance as a reasonable way to advance human health. However, actual implementation of this systems approach is not straightforward. While technology keeps advancing, our ability to accurately interpret the complexity of human biology has not kept pace. Indeed, sometimes the case seems to be one of the deeper we investigate, the more we realize what we do not understand. Additionally, in developing ethical pharmaceuticals, a major issue is establishing the necessary level of confidence to extrapolate from a series of endpoint measurements to accurately predict beneficial and/or potentially adverse responses in the diverse population of patients. The evidentiary standard for acceptance of new models and biomarkers in clinical practice is necessarily high, although the concept of “fit-for-purpose” may help expedite the application of new knowledge in specific clinical situations. This chapter will present a view of both the progress and hurdles to applying systems toxicology to drug development in a regulated environment. \u0000 \u0000 \u0000Keywords: \u0000 \u0000systems toxicology; \u0000drug development; \u0000biomarkers; \u0000clinical translation; \u0000pre-clinical; \u0000pathways; \u0000review; \u0000genomics; \u0000metabolomics; \u0000proteomics","PeriodicalId":325382,"journal":{"name":"General, Applied and Systems Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129905689","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: 0

Systems Modeling in Developmental Toxicity 发育毒性的系统建模

General, Applied and Systems Toxicology Pub Date : 2011-09-15 DOI: 10.1002/9780470744307.GAT236

T. Knudsen, R. Dewoskin

{"title":"Systems Modeling in Developmental Toxicity","authors":"T. Knudsen, R. Dewoskin","doi":"10.1002/9780470744307.GAT236","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT236","url":null,"abstract":"High-throughput or high-content studies are now providing a rich source of data that can be applied to in vitro profiling of chemical compounds for biological activity and potential in vivo toxicity. EPA's ToxCast™ project, and the broader Tox21 consortium, as well as other projects worldwide, are providing high-throughput and high-content screening data (HTS-HCS) focusing on the in vitro targets and cellular bioactivity profiles for thousands of chemical compounds in commerce or entering the environment. A goal of chemical profiling is to rapidly identify and efficiently classify signatures of biological activity that are potentially diagnostic of in vivo toxicities using automated technologies. Predictive modeling of developmental toxicity faces several challenges: correlating in vitro concentration–response with internal dose–response kinetics; understanding how in vitro bioactivity profiles extrapolate from one cell-type or technology platform to another; and linking individual targets of in vitro bioactivity to complex signatures associated with pathways of in vivo toxicity. Toxicity in the intact organism is an expression of complex and interwoven events that follow from cellular perturbations. As such, multicellular computer models known as ‘virtual tissues’ that recapitulate developmental events can provide a technology platform to simulate non-linear behaviors of dynamical systems and to model perturbations. A virtual embryo, for example, might be envisaged as a toolbox of computational (in silico) models that execute morphogenetic programs to simulate developmental toxicity. \u0000 \u0000 \u0000Keywords: \u0000 \u0000computational toxicology; \u0000high-throughput; \u0000screening; \u0000developmental toxicity; \u0000chemical profiling; \u0000toxicity pathways; \u0000predictive models; \u0000risk assessment; \u0000mechanistic models; \u0000systems biology; \u0000virtual tissues","PeriodicalId":325382,"journal":{"name":"General, Applied and Systems Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126986048","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: 5

Toxicity of Selenium Compounds and Nano‐Selenium Particles 硒化合物和纳米硒颗粒的毒性

General, Applied and Systems Toxicology Pub Date : 2011-09-15 DOI: 10.1002/9780470744307.GAT243

Jinsong Zhang, J. Spallholz

{"title":"Toxicity of Selenium Compounds and Nano‐Selenium Particles","authors":"Jinsong Zhang, J. Spallholz","doi":"10.1002/9780470744307.GAT243","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT243","url":null,"abstract":"Selenium is a necessary dietary constituent of at least 25 human selenoproteins and enzymes all containing selenocysteine. In excessive amounts, all selenium compounds become toxic in a dose-dependent fashion to cells in vitro and to the primary target tissue of chronic selenium toxicity, the liver. Elemental selenium of zero valence state has long been considered to be biologically inert. With bovine serum albumin or other dispersant agents such as polysaccharide, biologically active nano-selenium particles (Nano-Se) are formed from sodium selenite and glutathione. Different from the biologically inert black elemental selenium with coarse size, red Nano-Se manifests toxicity which conforms to the concern of nanotoxicity. However, compared with selenium compounds such as sodium selenite, selenomethionine and Se-methylselenocysteine, Nano-Se is not compromised in increasing the activities of selenoenzymes including glutathione peroxidase and thioredoxin reductase at nutritional levels and phase 2 detoxification enzymes such as glutathione S-transferase at supranutritional levels, but exhibits much lower toxicities. Nano-Se is thus a potential selenium source with a prominent characteristic of lower toxicity for supplementation. \u0000 \u0000 \u0000Keywords: \u0000 \u0000toxicity; \u0000selenite; \u0000selenomethionine; \u0000Se-methylselenocysteine; \u0000nano-selenium particles","PeriodicalId":325382,"journal":{"name":"General, Applied and Systems Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133649698","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: 34

Cardiac Toxicity of Anthracyclines 蒽环类药物的心脏毒性

General, Applied and Systems Toxicology Pub Date : 2009-12-15 DOI: 10.1002/9780470744307.GAT177

R. Olson, B. Cusack

引用次数: 1

Endocrine Disruption in Toxic Responses 毒性反应中的内分泌干扰

General, Applied and Systems Toxicology Pub Date : 2009-12-15 DOI: 10.1002/9780470744307.GAT018

S. Kitamura, K. Sugihara, Kazuo Nakamura, Y. Kotake, A. Kashiwagi, N. Fujimoto

引用次数: 0