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Sökning: WFRF:(Kleinjans Jos C. S.) > Toxicogenomics dire...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00008704naa a2200889 4500
001oai:research.chalmers.se:1976650f-4775-438d-b329-8ec0ea3f7fd4
003SwePub
008171008s2014 | |||||||||||000 ||eng|
0247 a https://doi.org/10.1007/s00204-014-1400-x2 DOI
0247 a https://research.chalmers.se/publication/2102462 URI
040 a (SwePub)cth
041 a engb eng
042 9 SwePub
072 7a art2 swepub-publicationtype
072 7a ref2 swepub-contenttype
1001 a Grinberg, Mariannau Technische Universität Dortmund4 aut
2451 0a Toxicogenomics directory of chemically exposed human hepatocytes
264 c 2014-11-16
264 1b 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 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Farmakologi och toxikologi0 (SwePub)301022 hsv//swe
650 7a 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
7001 a Stoeber, Regina M.u Leibniz Research Centre for Working Environment and Human Factors at the University of Dortmund4 aut
7001 a Edlund, K.u Leibniz Research Centre for Working Environment and Human Factors at the University of Dortmund4 aut
7001 a Rempel, Eugenu Technische Universität Dortmund4 aut
7001 a Godoy, Patriciou Leibniz Research Centre for Working Environment and Human Factors at the University of Dortmund4 aut
7001 a Reif, Raymondu Leibniz Research Centre for Working Environment and Human Factors at the University of Dortmund4 aut
7001 a Widera, Agatau Leibniz Research Centre for Working Environment and Human Factors at the University of Dortmund4 aut
7001 a Madjar, Katrinu Technische Universität Dortmund4 aut
7001 a Schmidt-Heck, Wolfgangu Hans-Knoll-Institute (HKI)4 aut
7001 a Marchan, Rosemarieu Leibniz Research Centre for Working Environment and Human Factors at the University of Dortmund4 aut
7001 a Sachinidis, Agapiosu Universität zu Köln,University of Cologne4 aut
7001 a Spitkovsky, Dimitryu Universität zu Köln,University of Cologne4 aut
7001 a Hescheler, Jurgenu Universität zu Köln,University of Cologne4 aut
7001 a Carmo, Helenau Universidade do Porto,University of Porto4 aut
7001 a Arbo, Marcelo D.u Universidade do Porto,University of Porto4 aut
7001 a van de Water, Bobu Universiteit Leiden (UL),Leiden University (UL)4 aut
7001 a Wink, Stevenu Universiteit Leiden (UL),Leiden University (UL)4 aut
7001 a Vinken, Mathieuu Vrije Universiteit Brüssel (VUB),Vrije Universiteit Brussel (VUB)4 aut
7001 a Rogiers, Verau Vrije Universiteit Brüssel (VUB),Vrije Universiteit Brussel (VUB)4 aut
7001 a Escher, Sylviau Fraunhofer Institut fur Toxikologie und Experimentelle Medizin - ITEM4 aut
7001 a Hardy, Barry4 aut
7001 a Mitic, Dragana4 aut
7001 a Myatt, Glennu Leadscope4 aut
7001 a Waldmann, Tanjau Universität Konstanz,University of Konstanz4 aut
7001 a Mardinoglu, Adil,d 1982u Chalmers tekniska högskola,Chalmers University of Technology4 aut0 (Swepub:cth)adilm
7001 a Damm, Georgu Charité Universitätsmedizin Berlin,Charité University Medicine Berlin4 aut
7001 a Seehofer, Danielu Charité Universitätsmedizin Berlin,Charité University Medicine Berlin4 aut
7001 a Nuessler, Andreasu Eberhard Karls Universität Tübingen,Eberhard Karls University of Tübingen4 aut
7001 a Weiss, Thomas S.u Universität Regensburg,University of Regensburg4 aut
7001 a Oberemm, Axelu Bundesinstitut Fuer Risikobewertung4 aut
7001 a Lampen, Alfonsu Bundesinstitut Fuer Risikobewertung4 aut
7001 a Schaap, Mirjam M.u Netherlands National Institute for Public Health & the Environment4 aut
7001 a Luijten, Mirjamu Netherlands National Institute for Public Health & the Environment4 aut
7001 a van Steeg, Harryu Netherlands National Institute for Public Health & the Environment4 aut
7001 a Thasler, Wolfgang E.4 aut
7001 a Kleinjans, Jos C. S.u Universiteit Maastricht,Maastricht University4 aut
7001 a Stierum, Rob H.u Nederlandse Organisatie voor toegepast-natuurwetenschappelijk onderzoek (TNO),Netherlands Organisation for Applied Scientific Research (TNO)4 aut
7001 a Leist, Marcelu Universität Konstanz,University of Konstanz4 aut
7001 a Rahnenfuehrer, Joergu Technische Universität Dortmund4 aut
7001 a Hengstler, Jan G.u Leibniz Research Centre for Working Environment and Human Factors at the University of Dortmund4 aut
7102 a Technische Universität Dortmundb Leibniz Research Centre for Working Environment and Human Factors at the University of Dortmund4 org
7730 t Archives of Toxicologyd : Springer Science and Business Media LLCg 88:12, s. 2261-2287q 88:12<2261-2287x 1432-0738x 0340-5761
8564 u http://dx.doi.org/10.1007/s00204-014-1400-xy FULLTEXT
8564 u https://kops.uni-konstanz.de/bitstream/123456789/29404/1/Leist_0-264490.pdf
8564 8u https://doi.org/10.1007/s00204-014-1400-x
8564 8u https://research.chalmers.se/publication/210246

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