Molecular Epidemiology of Atrazine's Hormonal Effects

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DESCRIPTION (Provided by Applicant) The candidate is a Behavioral Epidemiologist with 8 years of experience in conducting population based descriptive and experimental studies. The application describes a 5-year career development plan that will provide the candidate with the formal training and laboratory research experience necessary for her development as an independent investigator in molecular epidemiology of chemically related reproductive diseases. The candidate's long-term career objective is to develop an academic program of research that combines epidemiologic, molecular and genetic principles to study the complex associations of genes and environments factors in the etiology of reproductive diseases. The training component includes mentorship by an occupational molecular epidemiologist, a molecular biologist, and an environmental biostatistician; completion of advanced courses in molecular biology and genetic epidemiology; and six-month rotations annually in an occupational molecular epidemiology laboratory and a NIEHS Center Molecular Imaging and Analysis Facility. The research component describes a prospective investigation of exposure to the s-triazine herbicide, atrazine and effects on reproductive hormone production among male pesticide applicators. Atrazine is the most commonly used pesticide in agriculture (68 -73 million lbs. used in 1995). It is hypothesized that atrazine acts through a hormonal pathway to effect reproductive hormone production. It is further hypothesized that allelic variants in the cytochrome P450, subfamily 1, polypeptide 2 (CYPlA2) gene effects atrazine metabolization and ultimately toxicity. Baseline serum samples will be collected from applicators and non-applicators prior to the pesticide application season and evaluated for male reproductive hormone levels including follicle stimulating hormone, luteinizing hormone, and testosterone. Baseline serum samples will genotyped for allelic variants in the CYPlA2 gene. Urine samples and self-reported application information will be collected from atrazine applicators after first atrazine application and evaluated for atrazine metabolites to establish exposure. Features of this design include efficient control for confounding exposures, determination of within subject hormone level variability pre-exposure, accurate exposure ascertainment, sufficient power to detect exposure related changes in reproductive indicators; and design efficiency to evaluate polymorphic influence on atrazine metabolization.