Project Summary (2000-2005)

The goal of this project is to develop and validate a series of mechanistically based cell bioassays/biomarkers for chemical detection and screening. Stably transfected cell lines are being developed which respond to one or more hormones with the induction of the expression of firefly luciferase or green fluorescent protein reporter genes. The endocrine disrupting activity of a given chemical(s), or a complex chemical mixture, then can be rapidly determined by examining its ability to activate/inhibit induction of reporter gene expression. Project investigators are measuring perturbations in gene expression by dioxin, arsenic and chromium in human keratinocytes, using subtractive hybridization and DNA array techniques, to identify a series of gene products (i.e. potential biomarkers of effect) whose expression is altered by these chemicals. Overall, these approaches not only take advantage of the ability of a chemical to activate/inhibit intracellular receptor-mediated signaling events and gene expression, but the bioassays and biomarkers provide rapid mechanistically based screening systems to detect toxicants and toxicant exposure.