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  Testing chemical carcinogenicity by using a transcriptomics HepaRG-based model

Doktorova, T. Y., Yildirimman, R., Ceelen, L., Vilardell, M., Vanhaecke, T., Vinken, M., et al. (2014). Testing chemical carcinogenicity by using a transcriptomics HepaRG-based model. Experimental and Clinical Sciences Journal (EXCLI Journal), 13, 623-637.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0001-01C4-0 Version Permalink: http://hdl.handle.net/21.11116/0000-0001-01C5-F
Genre: Journal Article

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© 2014 Doktorova et al

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 Creators:
Doktorova, Tatyana Y. , Author
Yildirimman, Reha1, Author              
Ceelen, Liesbeth , Author
Vilardell, Mireia2, Author              
Vanhaecke, Tamara , Author
Vinken, Mathieu , Author
Ates, Gamze , Author
Heymans, Anja, Author
Gmuender, Hans, Author
Bort, Roque , Author
Corvi, Raffaella , Author
Phrakonkham, Pascal , Author
Li, Ruoya, Author
Mouchet, Nicolas , Author
Chesne, Christophe , Author
van Delft, Joost , Author
Kleinjans, Jos, Author
Castell, Jose, Author
Herwig, Ralf1, Author              
Rogiers, Vera , Author
Affiliations:
1Bioinformatics (Ralf Herwig), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479648              
2Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              

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Free keywords: HepaRG cell line; gene expression profiling; genotoxic carcinogens; liver-based in vitro models; non-genotoxic carcinogens; pathways-based analysis
 Abstract: The EU FP6 project carcinoGENOMICS explored the combination of toxicogenomics and in vitro cell culture models for identifying organotypical genotoxic- and non-genotoxic carcinogen-specific gene signatures. Here the performance of its gene classifier, derived from exposure of metabolically competent human HepaRG cells to prototypical non-carcinogens (10 compounds) and hepatocarcinogens (20 compounds), is reported. Analysis of the data at the gene and the pathway level by using independent biostatistical approaches showed a distinct separation of genotoxic from non-genotoxic hepatocarcinogens and non-carcinogens (up to 88 % correct prediction). The most characteristic pathway responding to genotoxic exposure was DNA damage. Interlaboratory reproducibility was assessed by blindly testing of three compounds, from the set of 30 compounds, by three independent laboratories. Subsequent classification of these compounds resulted in correct prediction of the genotoxicants. As expected, results on the non-genotoxic carcinogens and the non-carcinogens were less predictive. In conclusion, the combination of transcriptomics with the HepaRG in vitro cell model provides a potential weight of evidence approach for the evaluation of the genotoxic potential of chemical substances.

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Language(s): eng - English
 Dates: 2014-05-28
 Publication Status: Published online
 Pages: 15
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: PMC: PMC4464292
PMID: 26417288
 Degree: -

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Title: Experimental and Clinical Sciences Journal (EXCLI Journal)
Source Genre: Journal
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Publ. Info: Dortmund : Leibniz Research Centre for Working Environment and Human Factors
Pages: - Volume / Issue: 13 Sequence Number: - Start / End Page: 623 - 637 Identifier: ISSN: 1611-2156