Custom cDNA microarrays; technologies and applications

Abstract Technologies designed to characterise genes and their products on a discovery scale are now having an impact on many areas of biology, including toxicology. A number of platforms exist which measure changes in expression of potentially thousands of genes simultaneously. These approaches, when applied to toxicology, are termed ‘toxicogenomics’ and promise to greatly facilitate mechanism-based research on toxicant action with the longer term possibility of assisting in the identification of potential toxicity issues earlier in the development of new pharmaceutical, agrochemical and chemical products. An example of such a platform developed in our laboratory is ToxBlot II, a custom microarray containing cDNAs representing 12 564 human genes chosen on the basis of their potential relevance to a broad range of toxicities. ToxBlot II can assist in characterising many outcomes including processes as diverse as immune system response, receptor biology, signal transduction, protein modification, membrane transport, growth and development, metabolism, oxidative stress and regulation of the cell cytoskeleton. Furthermore, ToxBlot II allows the simultaneous expression profiling of genes representing entire cellular pathways, facilitating a very detailed investigation of potential mechanisms of toxicity. Our laboratory is applying this and other custom microarrays to many areas of toxicology, including endocrine disruption, receptor biology, stress response and the effect of toxicants on immune function. Such approaches can be particularly valuable when used in conjunction with ‘functional genomics’ such as transgenic or knockout models.