General, Applied and Systems Toxicology最新文献_第4页

Sequencing Technology Advances and Toxicology 测序技术进展与毒理学

General, Applied and Systems Toxicology Pub Date : 2011-09-15 DOI: 10.1002/9780470744307.GAT231

L. Ratnasinghe

引用次数: 0

Systems Toxicology: A Valuable Tool for Early Prediction and Mechanistic Assessment of Liver Toxicity of Food‐Related Products 系统毒理学:食品相关产品肝毒性早期预测和机制评估的宝贵工具

General, Applied and Systems Toxicology Pub Date : 2011-09-15 DOI: 10.1002/9780470744307.GAT211

S. Sahu

{"title":"Systems Toxicology: A Valuable Tool for Early Prediction and Mechanistic Assessment of Liver Toxicity of Food‐Related Products","authors":"S. Sahu","doi":"10.1002/9780470744307.GAT211","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT211","url":null,"abstract":"The review of literature demonstrates that systems toxicology is a valuable tool for early prediction and mechanistic assessment of liver toxicity. It will provide accurate molecular information for toxicity hazard and risk assessment in relatively short period of time. This technology will find very useful applications in food safety. It is an excellent tool for quick screening of hepatotoxic potential of food-related products that occur naturally or that are added deliberately to the foods and dietary supplements. The published reports show the value of omics technologies in combination with classical histopathology and biochemical assays providing a powerful tool for accurate assessment of “predictive” and “mechanistic” hepatotoxicity. The systems toxicology in vitro offers a powerful cost-effective tool for faster high-throughput toxicity testing. It can be effectively used for high-throughput screening of food-related products for potential hepatotoxicity. \u0000 \u0000 \u0000Keywords: \u0000 \u0000hepatotoxicity; \u0000in vitro toxicity; \u0000systems toxicology; \u0000risk assessment; \u0000omics technology","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":"130605640","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

Unravelling Sex Differences in Drug‐Induced Liver Injury 揭示药物性肝损伤的性别差异

General, Applied and Systems Toxicology Pub Date : 2011-09-15 DOI: 10.1002/9780470744307.GAT226

W. Tong, Q. Shi, W. Salminen, Minjun Chen, H. Fang, A. Suzuki, D. Mendrick

{"title":"Unravelling Sex Differences in Drug‐Induced Liver Injury","authors":"W. Tong, Q. Shi, W. Salminen, Minjun Chen, H. Fang, A. Suzuki, D. Mendrick","doi":"10.1002/9780470744307.GAT226","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT226","url":null,"abstract":"Liver toxicity accounts for 40% of failed drugs in clinical studies and approximately 21% of drugs that are removed from the market. It is suspected that drug-induced liver injury (DILI) is more common in females, thus impacting women's health to a higher degree. However, it is unclear how common this potential sex-based sensitivity may be and the mechanisms underlying the differences. High-content and high-throughput molecular technologies such as DNA microarrays have contributed significantly to the understanding of health and disease at the molecular level. In 2001, DNA microarray studies began to emerge to investigate sex-associated liver gene expression profiles under physiological and pathological conditions. This review is an analysis of clinical reports published to date to determine the weight of evidence in support of sex-biased sensitivity to DILI. Sex differences related to disease susceptibility/progression and adverse drug events are discussed at the molecular level with emphasis on genomic data in an attempt to place the evidence in a biological context. \u0000 \u0000 \u0000Keywords: \u0000 \u0000DILI; \u0000sex difference; \u0000genomics; \u0000drug-induced liver injury","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":"133542471","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: 1

Mechanistic Investigation of EMD335823s Hepatotoxicity Using Multiple Omics Profiling Technologies 利用多组学分析技术研究EMD335823s肝毒性的机制

General, Applied and Systems Toxicology Pub Date : 2011-09-15 DOI: 10.1002/9780470744307.GAT224

Alexandra Sposny, C. Schmitt, P. Hewitt

{"title":"Mechanistic Investigation of EMD335823s Hepatotoxicity Using Multiple Omics Profiling Technologies","authors":"Alexandra Sposny, C. Schmitt, P. Hewitt","doi":"10.1002/9780470744307.GAT224","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT224","url":null,"abstract":"We have used modern omics technologies (including Toxicogenomics, proteomics, metabonomics and profiling from FFPE tissues) to ascertain whether a systems biology approach would improve our understanding of the mechanism of toxicity of a compound. \u0000 \u0000 \u0000 \u0000Wistar rats were treated for up to 14 days with a non-toxic dose (15 mg kg−1) or a high dose (350 mg kg−1) of a known hepatotoxic compound (EMD 335823), chosen to ensure significant hepatotoxicity (liver necrosis, fibrosis, and bile duct necrosis/hyperplasia). \u0000 \u0000 \u0000 \u0000Genomics, proteomics, and metabonomics identified animals with the most severe effects, in good agreement with pathological findings. Protein expression changes correlated well with gene expression changes, indicating that EMD 335823 regulated PPARα signaling. EMD 335823 is an aldose reductase inhibitor resulting in increased glucose metabolism and alterations in fatty acid metabolism. These disturbances result in lower energy resources, contributing to the pathogenesis of liver damage. Proteomics and metabonomics also showed clear separation of the most severely affected animals, although the limited numbers of molecules identified could not reveal the mechanism of toxicity alone. \u0000 \u0000 \u0000 \u0000The combination of omics technologies allowed a more detailed analysis and identification of potential mechanisms of action, improving the overall understanding of the compounds toxicity. Additionally, there are indications that a compound-specific signature was visible earlier, when no histopathological changes occurred. \u0000 \u0000 \u0000Keywords: \u0000 \u0000cross-omics comparison; \u0000genomics; \u0000hepatotoxicity; \u0000metabonomics; \u0000proteomics; \u0000systems toxicology","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":"131323089","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

Multifunctional Nanomaterials for Biomedical Applications: The Onset of Nanomedicine 生物医学用途的多功能纳米材料:纳米医学的开始

General, Applied and Systems Toxicology Pub Date : 2011-09-15 DOI: 10.1002/9780470744307.GAT241

Yang Xu, M. Mahmood, A. Biris

引用次数: 0

Toxicology of Engineered Metal Nanoparticles 工程金属纳米颗粒毒理学

General, Applied and Systems Toxicology Pub Date : 2011-09-15 DOI: 10.1002/9780470744307.GAT240

G. Bernardini, A. Cattaneo, E. Sabbioni, M. Gioacchino, M. Chiriva-Internati, R. Gornati

引用次数: 9

Toxicogenomics — Applications in Systems Toxicology 毒物基因组学-在系统毒理学中的应用

General, Applied and Systems Toxicology Pub Date : 2011-09-15 DOI: 10.1002/9780470744307.GAT201

P. Joseph

{"title":"Toxicogenomics — Applications in Systems Toxicology","authors":"P. Joseph","doi":"10.1002/9780470744307.GAT201","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT201","url":null,"abstract":"Human exposure to toxic chemicals is almost unavoidable. The toxicity owing to human exposure to chemicals may result in adverse health effects such as illnesses and even death. It is therefore important to determine whether human exposure to chemicals may result in toxicity and, if so, to obtain a full understanding of the mechanism(s) underlying the toxicity. Recent developments in genomics and their application in toxicology (toxicogenomics) have facilitated a better understanding of chemical toxicity. Unlike traditional toxicity studies, toxicogenomics studies have the potential to detect toxicity pre-clinically (before the onset of clinical manifestations of toxicity) and this may have implications even in predicting the toxicity of chemicals. Recent studies have demonstrated the potential application of genomics-based toxicity determination in surrogate tissues such as blood, for monitoring human exposure to toxic chemicals. The potential of toxicogenomics in determining the toxicity of chemicals is best illustrated in the case of hepatotoxic chemicals. It is anticipated that toxicogenomics studies, in conjunction with the traditional toxicity determination approaches, may be useful to determine the systems toxicity of chemicals. \u0000 \u0000 \u0000Keywords: \u0000 \u0000blood; \u0000gene expression; \u0000hepatotoxicity; \u0000microarray; \u0000surrogate tissue; \u0000toxicogenomics","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":"122835515","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: 1

Application of DNA Microarray in Studies of Herbal Dietary Supplements DNA芯片技术在草药膳食补充剂研究中的应用

General, Applied and Systems Toxicology Pub Date : 2011-09-15 DOI: 10.1002/9780470744307.GAT225

Lei Guo, J. Fuscoe, P. Fu, N. Mei

{"title":"Application of DNA Microarray in Studies of Herbal Dietary Supplements","authors":"Lei Guo, J. Fuscoe, P. Fu, N. Mei","doi":"10.1002/9780470744307.GAT225","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT225","url":null,"abstract":"Herbal dietary supplements are used extensively worldwide and the consumption has dramatically increased in the United States in recent years. Although side effects of many herbal dietary supplements have been reported, safety assurance has not been addressed adequately and toxicological data on most herbal dietary supplements are lacking. To address the issue of human health protection, there are currently more than 30 herbal dietary supplements or active ingredients under study by the US National Toxicology Program (NTP). Herbal products often exhibit great variability in quality because of different processing methods, cultivation conditions, and harvest time, as well as the strain and species differences. Authentication of plant species used for preparation of herbal dietary supplements is a critical step of safety assurance. Botanical extracts differ from drugs in that they are mixtures of many active constituents. At present, there are no well-established methodologies for evaluating the toxicity or determining the toxic mechanisms of herbal plant extracts due to the complexity of chemical components. In this chapter, we describe the applications of DNA microarray for plant authentication and mechanistic studies of herbal dietary supplements. \u0000 \u0000 \u0000Keywords: \u0000 \u0000authentication of plant species; \u0000gene expression; \u0000herbal dietary supplements; \u0000microarray; \u0000pathway analysis; \u0000toxicity","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":"115596281","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

Effect of p53 Genotype on Gene Expression and DNA Adducts in ENU-Exposed Mice p53基因型对enu暴露小鼠基因表达及DNA加合物的影响

General, Applied and Systems Toxicology Pub Date : 2011-09-15 DOI: 10.1002/9780470744307.GAT203

R. Kulkarni, Dayton M Petibone, Ching-Wei Chang, James J. Chen, W. Tolleson, W. Melchior, M. Churchwell, F. Beland, S. Morris

{"title":"Effect of p53 Genotype on Gene Expression and DNA Adducts in ENU-Exposed Mice","authors":"R. Kulkarni, Dayton M Petibone, Ching-Wei Chang, James J. Chen, W. Tolleson, W. Melchior, M. Churchwell, F. Beland, S. Morris","doi":"10.1002/9780470744307.GAT203","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT203","url":null,"abstract":"P53, the tumour suppressor protein, plays a crucial role in the maintenance of genomic stability and is regarded as the ‘guardian of the genome’. To study tissue differences in p53 loss-of-function mutations, we investigated the effect of N-ethyl-N-nitrosourea (ENU), a highly potent mutagen, on gene expression at 4 and 24 h after exposure in the liver of p53+/+, p53+/− and p53−/− mice. Quantitative PCR and a targeted array were used to analyse the expression of 84 genes known to be involved in the p53 pathway at each time point. In addition, the levels of O6-ethyldeoxyguanosine, a major mutagenic DNA adduct, and the expression of Mgmt were determined at the 4- and 24-h time points. Significant differences were found among the three genotypes for the expression of the functional gene groupings of apoptosis, cell cycle, cell growth and proliferation and DNA repair. Furthermore, the loss of O6-ethyldeoxyguanosine from the DNA paralleled the expression of Mgmt in p53+/+ and p53+/− mice. The data from this study will aid in understanding variation in the DNA damage response across tissues and the biological effects of loss of function in p53. \u0000 \u0000 \u0000Keywords: \u0000 \u0000P53; \u0000ENU; \u0000gene expression; \u0000DNA Adducts","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":"122205933","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: 1

Epigenomic Analysis in Toxicology 毒理学中的表观基因组分析

General, Applied and Systems Toxicology Pub Date : 2011-09-15 DOI: 10.1002/9780470744307.GAT230

T. Ushijima, E. Okochi‐Takada, Hideyuki Takeshima

{"title":"Epigenomic Analysis in Toxicology","authors":"T. Ushijima, E. Okochi‐Takada, Hideyuki Takeshima","doi":"10.1002/9780470744307.GAT230","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT230","url":null,"abstract":"Epigenetic modifications are essential for development, differentiation, and reprogramming. They are inherited upon somatic cell replication, and include DNA methylation and histone modifications. Abnormality of epigenetic modifications is deeply involved in human cancers, as known by global hypomethylation and regional hypermethylation. Recent findings on the high fraction of cells affected in normal-appearing tissues indicated that epigenomic alterations are also involved in acquired disorders other than cancers. In spite of the deep involvement of epigenomic alterations in human diseases, only limited information is available for inducers of epigenetic changes, including aging, chronic inflammation, virus infection, disturbances in one carbon metabolism, and some chemicals. One of the reasons why a very limited number of chemicals are known as inducers of epigenetic alterations (epimutagens) is the lack of a sufficiently convenient and sensitive assay system. Toxicological considerations from the viewpoint of epigenomics are critically important, and epigenomic toxicology has just started. \u0000 \u0000 \u0000Keywords: \u0000 \u0000epigenetics; \u0000DNA methylation; \u0000histone modification; \u0000epigenome; \u0000cancer; \u0000epimutation; \u0000epimutagen","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":"116689025","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