The Agricultural Health Study (AHS) associated exposure to certain pesticides with increased prostate cancer risk in individuals with a first-degree family history of prostate cancer. These findings indicate that exposure to these environmental contaminants may interact with a genetic predisposition toward prostate cancer, but the biologic mechanism(s) by which this might occur remain unclear. This information is critical not only for better defining the risks posed by these pesticides for farm workers and others exposed to these chemicals, but also may advance our understanding of prostate cancer progression in the general population. Experimental exploration of the mechanistic links between pesticide exposure and prostate cancer progression will be difficult in humans. Therefore, the objective of this proposal is to test whether exposure to organophosphorothioates accelerates prostate cancer progression in a mouse model genetically predisposed to develop premalignant prostate lesions (B6:PTEN/luc) in order to establish an experimental platform for exploring these links.