Molecular Epidemiology of Atrazine's Hormonal Effects

描述（申请人提供） 候选人是一名行为流行病学家，具有8年的经验， 进行基于人口的描述性和实验性研究。 的 申请描述了一个5年的职业发展计划，将提供 具有正式培训和实验室研究经验的候选人 作为一名独立的分子生物学研究者， 化学相关生殖疾病的流行病学。 候选人的 长期的职业目标是发展一个学术研究计划， 结合流行病学、分子和遗传学原理来研究复杂的 生殖系统疾病病因学中基因与环境因素的关系 疾病 培训内容包括由职业培训师提供指导， 分子流行病学家、分子生物学家和环境学家 生物统计学家;完成分子生物学高级课程， 遗传流行病学;以及每年在一个职业 分子流行病学实验室和NIEHS分子成像中心， 分析设施。 研究部分描述了一个前景 对均三嗪类除草剂阿特拉津的暴露及其对 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 - 73百万磅）。用于 1995年）。 据推测，阿特拉津通过激素途径起作用， 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（CYP 1A 2）中的等位基因变体 基因影响阿特拉津的代谢并最终影响毒性。 基线血清 将从施用者和非施用者处收集样本， 农药施用季节和雄性生殖激素评价 水平，包括促卵泡激素，促黄体激素， 睾酮. 基线血清样本将进行等位基因变体的基因分型， CYP 1A 2基因。 尿液样本和自我报告的申请信息将 在首次施用阿特拉津后从阿特拉津施用者处收集， 评估阿特拉津代谢物以确定暴露量。 这间 设计包括对混杂暴露的有效控制， 暴露前受试者内激素水平变异性，准确暴露 有足够的把握度来检测暴露相关的变化， 繁殖指标和设计效率，以评估多态性 对阿特拉津代谢影响。

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.