The Principles and Practice of Toxicogenomics: Applications and Opportunities

The last decade has seen major developments in large-scale genome sequencing and in the development of technical platforms to support this. Several genomes, such as yeast (DeRisi et al., 1997), have now been completely sequenced and the sequencing of the entire human genome is anticipated to be completed early in this decade, as a result of major effort in both the academic and industrial sectors. The availability of both the sequence information for many thousands of genes and, in many cases, physical clones of the coding regions of these genes, has allowed the construction of gene microarrays that enable quantitative measurement of the transcriptional activity of potentially tens of thousands of genes in biological samples (Schena et al., 1995). Microarray technology promises to revolutionize investigative biology (Khan et al., 1999), including drug discovery (Marton et al., 1998). Application of genomics to toxicology, toxicogenomics, may also yield a number of substantial dividends, including assisting predevelopment toxicology by facilitating more rapid screens for compound toxicity; allowing compound selection decisions to be based on safety as well as efficacy; the provision of new research leads; a more detailed appreciation of molecular mechanisms of toxicity; and an enhanced ability to extrapolate accurately between experimental animals and humans in the context of risk assessment. In this article, we provide a brief overview of microarray technology and its applications to mechanistic and predictive toxicology research, outlining both the strengths and limitations of this approach.