Sökning: WFRF:(Sachinidis Agapios) > (2014) > Toxicogenomics dire...
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000 | 08704naa a2200889 4500 | |
001 | oai:research.chalmers.se:1976650f-4775-438d-b329-8ec0ea3f7fd4 | |
003 | SwePub | |
008 | 171008s2014 | |||||||||||000 ||eng| | |
024 | 7 | a https://doi.org/10.1007/s00204-014-1400-x2 DOI |
024 | 7 | a https://research.chalmers.se/publication/2102462 URI |
040 | a (SwePub)cth | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a art2 swepub-publicationtype |
072 | 7 | a ref2 swepub-contenttype |
100 | 1 | a Grinberg, Mariannau Technische Universität Dortmund4 aut |
245 | 1 0 | a Toxicogenomics directory of chemically exposed human hepatocytes |
264 | c 2014-11-16 | |
264 | 1 | b Springer Science and Business Media LLC,c 2014 |
520 | a A long-term goal of numerous research projects is to identify biomarkers for in vitro systems predicting toxicity in vivo. Often, transcriptomics data are used to identify candidates for further evaluation. However, a systematic directory summarizing key features of chemically influenced genes in human hepatocytes is not yet available. To bridge this gap, we used the Open TG-GATES database with Affymetrix files of cultivated human hepatocytes incubated with chemicals, further sets of gene array data with hepatocytes from human donors generated in this study, and publicly available genome-wide datasets of human liver tissue from patients with non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular cancer (HCC). After a curation procedure, expression data of 143 chemicals were included into a comprehensive biostatistical analysis. The results are summarized in the publicly available toxicotranscriptomics directory (http://wiki.toxbank.net/toxicogenomics-map/) which provides information for all genes whether they are up- or downregulated by chemicals and, if yes, by which compounds. The directory also informs about the following key features of chemically influenced genes: (1) Stereotypical stress response. When chemicals induce strong expression alterations, this usually includes a complex but highly reproducible pattern named 'stereotypical response.' On the other hand, more specific expression responses exist that are induced only by individual compounds or small numbers of compounds. The directory differentiates if the gene is part of the stereotypical stress response or if it represents a more specific reaction. (2) Liver disease-associated genes. Approximately 20 % of the genes influenced by chemicals are up- or downregulated, also in liver disease. Liver disease genes deregulated in cirrhosis, HCC, and NASH that overlap with genes of the aforementioned stereotypical chemical stress response include CYP3A7, normally expressed in fetal liver; the phase II metabolizing enzyme SULT1C2; ALDH8A1, known to generate the ligand of RXR, one of the master regulators of gene expression in the liver; and several genes involved in normal liver functions: CPS1, PCK1, SLC2A2, CYP8B1, CYP4A11, ABCA8, and ADH4. (3) Unstable baseline genes. The process of isolating and the cultivation of hepatocytes was sufficient to induce some stress leading to alterations in the expression of genes, the so-called unstable baseline genes. (4) Biological function. Although more than 2,000 genes are transcriptionally influenced by chemicals, they can be assigned to a relatively small group of biological functions, including energy and lipid metabolism, inflammation and immune response, protein modification, endogenous and xenobiotic metabolism, cytoskeletal organization, stress response, and DNA repair. In conclusion, the introduced toxicotranscriptomics directory offers a basis for a rationale choice of candidate genes for biomarker evaluation studies and represents an easy to use source of background information on chemically influenced genes. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Farmakologi och toxikologi0 (SwePub)301022 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Pharmacology and Toxicology0 (SwePub)301022 hsv//eng |
653 | a In vivo validation | |
653 | a Steatosis | |
653 | a Toxicotranscriptomics | |
653 | a Hepatotoxicity | |
653 | a Cirrhosis | |
653 | a Bioinformatics | |
653 | a Biomarker identification | |
653 | a Unsupervised clustering | |
653 | a SEURAT-1 | |
653 | a Hepatocellular cancer | |
700 | 1 | a Stoeber, Regina M.u Leibniz Research Centre for Working Environment and Human Factors at the University of Dortmund4 aut |
700 | 1 | a Edlund, K.u Leibniz Research Centre for Working Environment and Human Factors at the University of Dortmund4 aut |
700 | 1 | a Rempel, Eugenu Technische Universität Dortmund4 aut |
700 | 1 | a Godoy, Patriciou Leibniz Research Centre for Working Environment and Human Factors at the University of Dortmund4 aut |
700 | 1 | a Reif, Raymondu Leibniz Research Centre for Working Environment and Human Factors at the University of Dortmund4 aut |
700 | 1 | a Widera, Agatau Leibniz Research Centre for Working Environment and Human Factors at the University of Dortmund4 aut |
700 | 1 | a Madjar, Katrinu Technische Universität Dortmund4 aut |
700 | 1 | a Schmidt-Heck, Wolfgangu Hans-Knoll-Institute (HKI)4 aut |
700 | 1 | a Marchan, Rosemarieu Leibniz Research Centre for Working Environment and Human Factors at the University of Dortmund4 aut |
700 | 1 | a Sachinidis, Agapiosu Universität zu Köln,University of Cologne4 aut |
700 | 1 | a Spitkovsky, Dimitryu Universität zu Köln,University of Cologne4 aut |
700 | 1 | a Hescheler, Jurgenu Universität zu Köln,University of Cologne4 aut |
700 | 1 | a Carmo, Helenau Universidade do Porto,University of Porto4 aut |
700 | 1 | a Arbo, Marcelo D.u Universidade do Porto,University of Porto4 aut |
700 | 1 | a van de Water, Bobu Universiteit Leiden (UL),Leiden University (UL)4 aut |
700 | 1 | a Wink, Stevenu Universiteit Leiden (UL),Leiden University (UL)4 aut |
700 | 1 | a Vinken, Mathieuu Vrije Universiteit Brüssel (VUB),Vrije Universiteit Brussel (VUB)4 aut |
700 | 1 | a Rogiers, Verau Vrije Universiteit Brüssel (VUB),Vrije Universiteit Brussel (VUB)4 aut |
700 | 1 | a Escher, Sylviau Fraunhofer Institut fur Toxikologie und Experimentelle Medizin - ITEM4 aut |
700 | 1 | a Hardy, Barry4 aut |
700 | 1 | a Mitic, Dragana4 aut |
700 | 1 | a Myatt, Glennu Leadscope4 aut |
700 | 1 | a Waldmann, Tanjau Universität Konstanz,University of Konstanz4 aut |
700 | 1 | a Mardinoglu, Adil,d 1982u Chalmers tekniska högskola,Chalmers University of Technology4 aut0 (Swepub:cth)adilm |
700 | 1 | a Damm, Georgu Charité Universitätsmedizin Berlin,Charité University Medicine Berlin4 aut |
700 | 1 | a Seehofer, Danielu Charité Universitätsmedizin Berlin,Charité University Medicine Berlin4 aut |
700 | 1 | a Nuessler, Andreasu Eberhard Karls Universität Tübingen,Eberhard Karls University of Tübingen4 aut |
700 | 1 | a Weiss, Thomas S.u Universität Regensburg,University of Regensburg4 aut |
700 | 1 | a Oberemm, Axelu Bundesinstitut Fuer Risikobewertung4 aut |
700 | 1 | a Lampen, Alfonsu Bundesinstitut Fuer Risikobewertung4 aut |
700 | 1 | a Schaap, Mirjam M.u Netherlands National Institute for Public Health & the Environment4 aut |
700 | 1 | a Luijten, Mirjamu Netherlands National Institute for Public Health & the Environment4 aut |
700 | 1 | a van Steeg, Harryu Netherlands National Institute for Public Health & the Environment4 aut |
700 | 1 | a Thasler, Wolfgang E.4 aut |
700 | 1 | a Kleinjans, Jos C. S.u Universiteit Maastricht,Maastricht University4 aut |
700 | 1 | a Stierum, Rob H.u Nederlandse Organisatie voor toegepast-natuurwetenschappelijk onderzoek (TNO),Netherlands Organisation for Applied Scientific Research (TNO)4 aut |
700 | 1 | a Leist, Marcelu Universität Konstanz,University of Konstanz4 aut |
700 | 1 | a Rahnenfuehrer, Joergu Technische Universität Dortmund4 aut |
700 | 1 | a Hengstler, Jan G.u Leibniz Research Centre for Working Environment and Human Factors at the University of Dortmund4 aut |
710 | 2 | a Technische Universität Dortmundb Leibniz Research Centre for Working Environment and Human Factors at the University of Dortmund4 org |
773 | 0 | t Archives of Toxicologyd : Springer Science and Business Media LLCg 88:12, s. 2261-2287q 88:12<2261-2287x 1432-0738x 0340-5761 |
856 | 4 | u http://dx.doi.org/10.1007/s00204-014-1400-xy FULLTEXT |
856 | 4 | u https://kops.uni-konstanz.de/bitstream/123456789/29404/1/Leist_0-264490.pdf |
856 | 4 8 | u https://doi.org/10.1007/s00204-014-1400-x |
856 | 4 8 | u https://research.chalmers.se/publication/210246 |
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