The European FP6 project carcinoGENOMICS aims to develop in vitro methods for assessing the carcinogenic potential of compounds, as an alternative to the bioassays for genotoxicity and carcinogenicity that are currently conducted in rodents. Questions over the relevance of animal studies to predict human risk, and how it would be possible to conduct sufficient in vivo experiments to meet upcoming regulatory requirements have driven forward research into high-throughput in vitro approaches.
The main objective of the project is to develop tests that can report on the carcinogenic potential and likely mode of carcinogenic action (genotoxic / non-genotoxic) of chemical compounds.
The work covers both human and rodent cell systems across the major target organs - liver, kidney, lung - and will generate parallel metabonomic and transcriptomic profiles describing the consequences of short-term incubation with representative chemicals in order to build predictive models of carcinogenicity.
Prediction of the mechanisms of chemical carcinogenesis in vivo will be made through extensive biostatistical analysis to define perturbed pathways and will require the development of novel chemometric tools.
The outcome of carcinoGENOMICS will be the components of a high-throughput screen for assessing chemcical carcinogenicity potential. High-throughput in vitro appraoches for carcinogenicity testing promise to improve the efficiency of chemical risk assessement and reduce the number and cost of animal testing in this area.
For more information, visit the carcinoGENOMICS website.
Key Recent Publications
Ellis JK, Chan PH, Doktorova T, Athersuch TJ, Cavill R, Vanhaecke T, Rogiers V, Vinken M, Nicholson JK, Ebbels TMD and others. 2010. Effect of the Histone Deacetylase Inhibitor Trichostatin A on the Metabolome of Cultured Primary Hepatocytes. Journal of Proteome Research 9(1):413-9.
Vinken M, Doktorova T, Ellinger-Ziegelbauer H, Ahr HJ, Lock E, Carmichael P, Roggen E, van Delft J, Kleinjans J, Castell J and others. 2008. The carcinoGENOMICS project: critical selection of model compounds for the development of omics-based in vitro carcinogenicity screening assays. Mutat Res 659(3):202-10.