Project Summary (2000-2006)

Project investigators are identifying and validating sensitive biomarkers of exposure, as well as characterizing molecular and cellular mechanisms for altered uterine, placental, and prostate function. The goal is to detect alterations in gene expression in human reproductive cell lines, which are mediated by contaminants commonly found at Superfund sites. In vitro models are being used to study the development and function of human placenta, uterus and prostate. To date the studies have focused on using 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), benzo(a)pyrene (BaP), and polychlorinated biphenyl (PCB) congeners as prototypes for defining mechanisms for aryl hydrocarbon receptor (AhR) dependent effects. AhR is important because it mediates transcription and has a direct impact on carcinogenesis, metabolism, endocrine regulation, and immune function. The hypothesis for this research is that TCDD and BaP alter growth regulatory networks, which are recognized as being important for proliferation, migration/invasiveness and hormone responsiveness. Additionally, research is being conducted to evaluate the effects of PCB congeners relevant to human exposure, which may have both AhR dependent and independent mechanisms of action. The final goal of the project is to investigate whether human prostate cell lines are targets for changes in proliferation, migration, and growth factor gene expression, which can be mechanisms for the promotion of prostate disease.