Molecular Epidemiology of Atrazine's Hormonal Effects

描述(由申请人提供) 应聘者是一名行为流行病学家，有8年的 进行以人口为基础的描述性和实验性研究。这个 申请描述了一项为期5年的职业发展计划，该计划将提供 有正规培训和实验室研究经验的候选人 对于她发展成为一名独立的分子研究员来说是必要的 化学相关生殖疾病的流行病学。候选人的 长期的职业目标是开发一个学术研究计划， 结合流行病学、分子和遗传学原理来研究这种复合体 生殖病因学中基因与环境因素的关系 疾病。培训部分包括职业指导。 分子流行病学家、分子生物学家和环境学家 生物统计学家；完成分子生物学和生物科学高级课程 遗传流行病学；以及职业生涯中每年六个月的轮换 分子流行病学实验室和NIEHS中心分子成像和 分析设施。研究部分描述了一个前景 S-三氮卓类除草剂阿特拉津的接触调查及对环境的影响 男性农药施用者生殖激素的产生。阿特拉津是 农业中最常用的杀虫剂(68-7300万磅。用于 1995年)。据推测，阿特拉津通过荷尔蒙途径作用于 影响生殖激素的产生。进一步假设 细胞色素P450亚家族1、多肽2的等位基因变异 基因影响阿特拉津的代谢，并最终产生毒性。基线血清 样本将在申请前从申请者和非申请者那里收集 农药使用季节及对雄性生殖激素的评价 水平包括卵泡刺激素、黄体生成素和 睾丸激素。基线血清样本将进行等位基因变异基因分型 CYPLA2基因。尿样和自我报告的申请信息将 在第一次使用阿特拉津后从阿特拉津涂抹器收集 评估阿特拉津代谢物以确定暴露情况。它的特点是 设计包括对混杂曝光的有效控制，确定 受试者体内激素水平在暴露前变化，准确暴露 确定，足够的能力来检测与暴露相关的变化 生殖指标；以及评估多态的设计效率 对阿特拉津代谢的影响。

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.