Cross-species comparative toxicogenomics as an aid to safety assessment.
Cross-species comparative toxicogenomics has the potential for improving the understanding of the different responses of animal models to toxicants at a molecular level. This understanding could then lead to a more accurate extrapolation of the risk posed by these toxicants to humans. Cross-species comparative studies have been carried out at the genomic sequence level and using microarrays to examine changes in global mRNA profiles. However, these studies face considerable bioinformatic challenges in terms of identifying which genes are truly orthologous across species. The resources to analyse such studies, in the context of such orthologues, beg improvement. Finally, the experimental design of such studies needs to be carefully considered to make their results fully interpretable. These issues are discussed, along with the current state-of-the-art cross-species comparative toxicogenomics in this review.
Mattes
William B
WB
Gene Logic, Gaithersburg, MD, USA. wmattes@c-path.org
D000818:Animals; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D013045:Species Specificity; D018675:Toxicity Tests / Q000379:methods*; D043922:Toxicogenetics / Q000379:methods*