Mini-review The carcinoGENOMICS project: Critical selection of model compounds for the development of omics-based in vitro carcinogenicity screening assays Mathieu Vinken a,1, *, Tatyana Doktorova a , Heidrun Ellinger-Ziegelbauer b , Hans-Ju ¨ rgen Ahr b , Edward Lock c , Paul Carmichael d , Erwin Roggen e , Joost van Delft f , Jos Kleinjans f , Jose ´ Castell g , Roque Bort g , Teresa Donato g , Michael Ryan h , Raffaella Corvi i , Hector Keun j , Timothy Ebbels j , Toby Athersuch j , Susanna-Assunta Sansone k , Philippe Rocca-Serra k , Rob Stierum l , Paul Jennings m , Walter Pfaller m , Hans Gmuender n , Tamara Vanhaecke a,1 , Vera Rogiers a a Department of Toxicology, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, B-1090 Brussels, Belgium b Bayer Healthcare AG, Department of Molecular and Genetic Toxicology, Aprather Weg 18a, 42096 Wuppertal, Germany c School of Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool L3 3AF, United Kingdom d Safety & Environmental Assurance Center, Unilever Colworth, Sharnbrook, Bedford MK44 1LQ, United Kingdom e Novozymes A/S, Krogshoejvej 36, DK 2880 Bagsvaerd, Denmark f Department of Health Risk Analysis and Toxicology, Maastricht University PO Box 616, 6200 MD Maastricht, The Netherlands g Unidad de Hepatologı´a Experimental, Centro de Investigacio ´n, University Hopital La Fe, Valencia, Spain h Department of Pharmacology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland i European Centre for the Validation of Alternative Methods (ECVAM), Institute for Health and Consumer Protection (IHCP), Joint Research Centre of the European Commission (JRC), Ispra, Italy j Department of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Faculty of Medicine, Imperial College London, London SW7 2AZ, United Kingdom k The European Bioinformatics Institute – European Molecular Biology Laboratory Outstation (EMBL-EBI), Wellcome Trust Genome Campus CB10 1SD, Cambridge Hinxton, United Kingdom l Business Unit Biosciences, TNO Quality of Life, P.O. Box 360, 3700 AJ, Zeist, The Netherlands m Division of Physiology, Department of Physiology and Medical Physics, Innsbruck Medical University, Innsbruck, Austria n Genedata AG, CH-4016 Basel, Switzerland Mutation Research 659 (2008) 202–210 ARTICLE INFO Article history: Received 30 January 2008 Received in revised form 2 April 2008 Accepted 21 April 2008 Available online 26 April 2008 Keywords: carcinoGENOMICS FP6 project REACH Chemical carcinogenesis ABSTRACT Recent changes in the European legislation of chemical-related substances have forced the scientific community to speed up the search for alternative methods that could partly or fully replace animal experimentation. The Sixth Framework Program project carcinoGENOMICS was specifically raised to develop omics-based in vitro screens for testing the carcinogenic potential of chemical compounds in a pan-European context. This paper provides an in-depth analysis of the complexity of choosing suitable reference compounds used for creating and fine-tuning the in vitro carcinogenicity assays. First, a number of solid criteria for the selection of the model compounds are defined. Secondly, the strategy followed, including resources consulted, is described and the selected compounds are briefly illustrated. Finally, limitations and problems encountered during the selection procedure are discussed. Since selecting an appropriate set of chemicals is a frequent impediment in the * Corresponding author. Tel.: +32 2 4774587; fax: +32 2 4774582. E-mail address: mvinken@vub.ac.be (M. Vinken). 1 These authors are postdoctoral research fellows of the Fund for Scientific Research Flanders (FWO-Vlaanderen), Belgium. Abbreviations: AhR, aryl hydrocarbon receptor; CA, chromosome aberration; CAS, Chemical Abstracts Service; ChEBI, Chemical Entities of Biological Interest; CYP, cytochrome P450; DCVC, S-(1,2-dichlorovinyl)-L-cysteine; ECOPA, European Consensus Platform on 3R-Alternatives; ECVAM, European Centre for the Validation of Alternative Methods; FP6, Sixth Framework Program; HPRT, hypoxanthine-guanine phosphoribosyltransferase; IARC, International Agency for Research on Cancer; Ki, kidney; Li, liver; Lu, lung; MLA, mouse lymphoma assay; MNT, micronucleus test; NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; NS, not specified; OECD, Organization for Economic Co-operation and Development; REACH, registration, evaluation and authorization of chemicals; UDS, unscheduled DNA synthesis; WP, work package. Contents lists available at ScienceDirect Mutation Research/Reviews in Mutation Research journal homepage: www.elsevier.com/locate/reviewsmr Community address: www.elsevier.com/locate/mutres 1383-5742/$ – see front matter . Crown Copyright ß 2008 Published by Elsevier B.V. All rights reserved. doi:10.1016/j.mrrev.2008.04.006