The application of toxicogenomics in predictive toxicology. Zacharewski, T.R.

In order to fully assess the effects of chronic and subchronic exposure to exogenous substances, both synthetic and natural, a more comprehensive understanding of the molecular, cellular and tissue level effects is required within the context of the whole organism and its genome. The rapid advancement of various genome projects has generated full or partial sequence data for thousands of genes in a number of different organisms. Following their completion, the goal will be to analyze the function of these genes and determine how they are regulated in a coordinated fashion to direct development, growth, differentiation, homeostasis, aging and the onset of disease. The availability of partial gene sequences has resulted in the development of array technology enabling scientists to simultaneously examine the totality of gene behavior in model systems. Toxicogenomics is an emerging field that utilizes array technology within predictive and discovery toxicology paradigms. It integrates the awesome potential of bioinfomatics and genomics with toxicology to assess and elucidate the mechanisms of action of known and suspected toxicants as well as drug candidates. This presentation will provide an overview of current efforts examining the effects of male endocrine disruptors on reproductive development, spermatogenesis and testicular gene expression. More specifically, the development of a relational database (dbTEST), the construction of a mouse testis cDNA/EST array and data analysis strategies will be discussed in relation to ongoing toxicogenomic studies.