Incorporating toxicogenomics into predictive and mechanistic toxicology: a case study. Zacharewski, T.R.

In order to fully assess the effects of chronic and subchronic exposure to synthetic and natural substances, a more comprehensive understanding of the molecular, cellular and tissue level effects is required within the context of the whole organism, its genome and its proteome. The rapid advancement of various genome projects has generated full or partial sequence data for thousands of genes in a number of different organisms. It is now possible to analyze the response of these genes following exposure to synthetic and natural substances and infer potential consequences. It has been proposed that toxicogenomics, an emerging field that integrates the awesome potential of bioinfomatics and genomics with toxicology, can be used to assess drug candidates and provide mechanistic information. This presentation will provide an overview of the strategies used to incorporate toxicogenomics into predictive and mechanistic toxicology. More specifically, the development of a relational database (dbZACH), the construction of model specific arrays and data analysis strategies will be discussed in relation to ongoing studies investigating the effects of exposure to estrogenic substances in different in vitro and in vivo models.