TCDD cell and gene targets in mouse developing prostate

University Of Rochester, Rochester NY

Investigators

Abstract

[unreadable] DESCRIPTION (provided by applicant): The long term goal of this proposal is to elucidate the pathogenesis of TCDD toxicity in the developing ventral prostate (VP). Interest in the role of environmental chemicals in the onset and/or progression of human diseases has been expressed by observations in wildlife, suggesting a link between reproductive disruption and environmental pollutants. TCDD, an ubiquitous environmental contaminant, is believed to be involved in these reproductive disruptions. The initial step, TCDD binding, and toxic endpoint, abnormal VP development, are known, however, the initial cell types and genes involved in the pathogenesis are not well established. The overall hypothesis for this proposal is that TCDD-induced aryl hydrocarbon receptor (AhR) transcriptional activity directly affects specific cells and genes near the urogenital sinus resulting in aberrant VP development. Using AhR-responsive reporter gene transgenic mice, cells with TCDD-induced AhR transcriptional activity will be identified and isolated by laser capture microdissection for microarray analysis. Genes involved in mesenchymal-epithelial interactions, critical for VP development, will be closely monitored. These studies will provide relevant information, i.e. identify direct cell and gene targets of TCDD, necessary for elucidating the pathogenesis of TCDD-induced toxicity in the developing VP. [unreadable] [unreadable] [unreadable]