Project description:We applied an effects-based approach to determine if the impact of specific chemicals in mixtures discharged by waste water treatment plants could be linked to well-defined gene expression changes in exposed fish. Fathead minnows were deployed in cages for 2, 4, or 8 days at three locations near two WWTP discharge sites in the Saint Louis Bay, Duluth, MN and one upstream control site. The impact of 51 chemicals detected in the surface water on gene expression in ovaries of caged fish was determined using exposure activity ratios, existing knowledge on chemical:gene relationships, and analysis of gene expression co-variance with surface water chemistry. Thirty-two chemicals could be linked to gene expression and 12 were confirmed by other sources such as the Comparative Toxicogenomics Database (CTD). Chemical:gene associations determined by co-variation were supported by exposure activity ratios sufficient to cause biological effects, known chemical:gene associations from CTD, and upstream regulator analysis of the Ingenuity knowledge base. The analyses provided multiple lines of evidence that bisphenol A and estrone are likely sources of estrogenic effects on gene expression found at the study sites.
