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Transcriptomic resp...
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Doktorova, Tatyana Y.Department of Toxicology, Center for Pharmaceutical Research, Vrije Universiteit Brussel, Brussels, Belgium
(author)
Transcriptomic responses generated by hepatocarcinogens in a battery of liver-based in vitro models
- Article/chapterEnglish2013
Publisher, publication year, extent ...
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2013-02-07
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Oxford University Press,2013
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Numbers
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LIBRIS-ID:oai:DiVA.org:his-8429
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https://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-8429URI
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https://doi.org/10.1093/carcin/bgt054DOI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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As the conventional approach to assess the potential of a chemical to cause cancer in humans still includes the 2-year rodent carcinogenicity bioassay, development of alternative methodologies is needed. In the present study, the transcriptomics responses following exposure to genotoxic (GTX) and non-genotoxic (NGTX) hepatocarcinogens and non-carcinogens (NC) in five liver-based in vitro models, namely conventional and epigenetically stabilized cultures of primary rat hepatocytes, the human hepatoma-derived cell lines HepaRG and HepG2 and human embryonic stem cell-derived hepatocyte-like cells, are examined. For full characterization of the systems, several bioinformatics approaches are employed including gene-based, ConsensusPathDB-based and classification analysis. They provide convincingly similar outcomes, namely that upon exposure to carcinogens, the HepaRG generates a gene classifier (a gene classifier is defined as a selected set of characteristic gene signatures capable of distinguishing GTX, NGTX carcinogens and NC) able to discriminate the GTX carcinogens from the NGTX carcinogens and NC. The other in vitro models also yield cancer-relevant characteristic gene groups for the GTX exposure, but some genes are also deregulated by the NGTX carcinogens and NC. Irrespective of the tested in vitro model, the most uniformly expressed pathways following GTX exposure are the p53 and those that are subsequently induced. The NGTX carcinogens triggered no characteristic cancer-relevant gene profiles in all liver-based in vitro systems. In conclusion, liver-based in vitro models coupled with transcriptomics techniques, especially in the case when the HepaRG cell line is used, represent valuable tools for obtaining insight into the mechanism of action and identification of GTX carcinogens.
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Yildirimman, RehaDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany
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Vinken, MathieuDepartment of Toxicology, Center for Pharmaceutical Research, Vrije Universiteit Brussel, Brussels, Belgium
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Vilardell, MireiaDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany
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Vanhaecke, TamaraDepartment of Toxicology, Center for Pharmaceutical Research, Vrije Universiteit Brussel, Brussels, Belgium
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Gmuender, HansGenedata AG, Basel, Switzerland
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Bort, RoqueUnit of Experimental Hepathology, University Hospital La Fe Valencia, Spain / Faculty of Medicine, Department of Biochemistry and Molecular Biology, University of Valencia, Valencia, Spain
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Brolen, GabriellaCellectis, Göteborg, Sweden
(author)
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Holmgren, GustavHögskolan i Skövde,Institutionen för vård och natur,Forskningscentrum för Systembiologi,Cellectis, Göteborg, Sweden(Swepub:his)holq
(author)
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Li, RuoyaBiopredic International, Rennes, France
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Chesne, ChristopheBiopredic International, Rennes, France
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van Delft, JoostDepartment of Toxicogenomics, Maastricht University, Maastricht, The Netherlands
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Kleinjans, JosDepartment of Toxicogenomics, Maastricht University, Maastricht, The Netherlands
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Castell, JoseUnit of Experimental Hepathology, University Hospital La Fe Valencia, Spain / Faculty of Medicine, Department of Biochemistry and Molecular Biology, University of Valencia, Valencia, Spain
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Björquist, PetterCellectis, Göteborg, Sweden
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Herwig, RalfDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany
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Rogiers, VeraDepartment of Toxicology, Center for Pharmaceutical Research, Vrije Universiteit Brussel, Brussels, Belgium
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Department of Toxicology, Center for Pharmaceutical Research, Vrije Universiteit Brussel, Brussels, BelgiumDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany
(creator_code:org_t)
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In:Carcinogenesis: Oxford University Press34:6, s. 1393-14020143-33341460-2180
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