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Development of a high throughput genomics-based test for assessing genotoxic and carcinogenic properties of chemical compounds in vitro

Objective

The major aim of CARCINOGENOMICS is to develop in vitro methods for assessing the carcinogenic potential of compounds, as an alternative to current rodent bioassays for genotoxicity and carcinogenicity. The major goal is to develop a battery of mechanism-based in vitro tests accounting for various modes of carcinogenic action. These tests will be designed to cover major target organs for carcinogenic action e.g. the liver, the lung, and the kidney. The novel assays will be based on the application of "omics" technologies (i.e. genome-wide transcriptomics as well as metabonomics) to robust in vitro systems (rat/human), thereby also exploring stem cell technology, to generate "omic" responses from a well-defined set of model compounds causing genotoxicity and carcinogenicity. Phenotypic markers for genotoxic and carcinogenic events will be assessed for the purpose of anchoring gene expression modulations, metabolic profiles and mechanism pathways.
Through extensive biostatistics, literature mining, and analysis of molecular-expression datasets, differential genetic pathways will be identified capable of predicting mechanisms of chemical carcinogenesis in vivo. Furthermore, generated transcriptomic and metabonomic data will be integrated into a holistic understanding of systems biology, and applied to build an iterative in silico model of chemical carcinogenesis. Subsequently, predictive gene expression profiles, typically consisting of some 150-250 genes, will be loaded onto high throughput dedicated DNA-chips, thus accelerating the analysis of transcriptomic responses by a factor of 100. It is expected that the outcome of this project will generate a platform enabling the investigation of large numbers of compounds for their genotoxic and carcinogenic potential, as envisaged under the REACH initiative. This will contribute to speeding the identification of potential harmful substances to man, while lowering costs and reducing animal tests.

Call for proposal

FP6-2005-LIFESCIHEALTH-6
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Funding Scheme

IP - Integrated Project

Coordinator

MAASTRICHT UNIVERSITY
Address
Minderbroedersberg 4-6
616 Maastricht
Netherlands

Participants (18)

FUNDACION HOSPITAL UNIVERSITARIO LA FE
Spain
Address
Avda. Campanar 21
Valencia
VRIJE UNIVERSITEIT BRUSSEL
Belgium
Address
Pleinlaan 2
Brussel
CELLARTIS AB
Sweden
Address
Arvid Wallgrens Backe 20
Gothenburg
LEIDEN UNIVERSITY MEDICAL CENTER
Netherlands
Address
Albinusdreef 2
9600 Leiden
NATIONAL UNIVERSITY OF IRELAND, DUBLIN. UNIVERSITY COLLEGE DUBLIN
Ireland
Address
Dublin 4
Belfield
NOVOZYMES AS
Denmark
Address
Krogshoejvej 36
Bagsvaerd
IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY & MEDICINE
United Kingdom
Address
Exhibition Road, South Kensington Campus
London
ADVANCELL ADVANCED IN VITRO CELL TECHNOLOGIES, S.A.
Spain
Address
C/ Baldiri I Reixach, 10
Barcelona
EUROPEAN MOLECULAR BIOLOGY LABORATORY
Germany
Address
Meyerhofstrasse 1
Heidelberg
NETHERLANDS ORGANISATION FOR APPLIED SCIENTIFIC RESEARCH
Netherlands
Address
Schoemakerstraat 97
6060 Delft
MAX-PLANCK-GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN E.V.
Germany
Address
Hofgartenstr. 8
München
EUROPEAN COMMISSION - DG JRC-IHCP-ECVAM "DG JRC"
Belgium
Address
Rue De La Loi 200
Brussels
EUROPEAN CONSENSUS PLATFORM FOR ALTERNATIVES
Belgium
Address
Paul Deschanellaan 36-38
Brussels
UNILEVER UK CENTRAL RESOURCES LIMITED
United Kingdom
Address
Unilever House, 100 Victoria Embankment
London
INNSBRUCK MEDICAL UNIVERSITY
Austria
Address
Christoph-probst-platz
Innsbruck
GENEDATA AG
Switzerland
Address
Maulbeerstrasse 46
Basel
BIOPREDIC INTERNATIONAL SARL
France
Address
8-18 Rue Jean Pecker
Rennes
LIVERPOOL JOHN MOORES UNIVERSITY
United Kingdom
Address
Rodney House, 70, Mount Pleasant
Liverpool