Main Article Content
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.
Authors who publish in this journal agree to the following terms:
- The authors keep the copyright and grant the journal the right of first publication under the terms of the Creative Commons Attribution license, CC BY 4.0. This licencse permits unrestricted use, distribution and reproduction in any medium, provided that the original work is properly cited.
- The use of general descriptive names, trade names, trademarks, and so forth in this publication, even if not specifically identified, does not imply that these names are not protected by the relevant laws and regulations.
- Because the advice and information in this journal are believed to be true and accurate at the time of publication, neither the authors, the editors, nor the publisher accept any legal responsibility for any errors or omissions presented in the publication. The publisher makes no guarantee, express or implied, with respect to the material contained herein.
- The authors can enter into additional contracts for the non-exclusive distribution of the journal's published version by citing the initial publication in this journal (e.g. publishing in an institutional repository or in a book).