Title: Testing chemical carcinogenicity by using a transcriptomics HepaRG-based model?
Authors: DOKTOROVA TatyanaYILDIRIMMAN RehaCEELEN LiesbethVILARDELL MireiaVANHAECKE TamaraVINKEN MathieuATES GamzeHEYMANS AnjaGMUENDER HansBORT RoqueCORVI RaffaellaPHRAKONKHAM PASCALLI RuoyaMOUCHET NicolasCHESNE ChristopherVAN DELFT JoostKLEINJANS JosCASTELL JoseHERWIG RalfROGIERS Vera
Citation: EXCLI JOURNAL vol. 13 p. 623-637
Publisher: EXCLI JOURNAL MANAGING OFFICE
Publication Year: 2014
JRC N°: JRC88521
ISSN: 1611-2156
URI: http://www.excli.de/vol13/Doktorova_28052014_proof.pdf
http://publications.jrc.ec.europa.eu/repository/handle/JRC88521
Type: Articles in periodicals and books
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.
JRC Directorate:Institute for Health and Consumer Protection Historical Collection

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