EFFECTS OF PRIOR OR CONCURRENT DIELDRIN EXPOSURE ON TISSUE ATRAZINE METABOLISM

先前或同时接触狄氏剂对组织莠去津代谢的影响

• 批准号: 7381819
• 负责人: NIKOLAY M FILIPOV
• 金额: $ 3.57万
• 依托单位: MISSISSIPPI STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381819
• 关键词: EFFECTS; PRIOR; CONCURRENT; DIELDRIN; EXPOSURE

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Exposure to atrazine, one of the widely used herbicides in the United States, has been associated with deleterious effects on various organ systems. However, in order to establish the human health relevancy of these studies, tissue dosimetry and pharmacokinetics studies are needed. In addition, atrazine metabolism is dependent in large measure upon the activities of cytochrome P450 (CYP) mono-oxygenases. Certain pesticides that are now banned, but still widely present in the environment, such as the insecticide dieldrin, are known CYP inducers. The persistence of dieldrin and the high use of atrazine, increase the likelihood of exposure to these two pesticides in combination. Existing analytical methods to analyze atrazine in biological matrices have various drawbacks. We have recently developed an LC-MS method to analyze atrazine and all of its major mammalian metabolites in mouse plasma and urine. In this project, we will optimize this method for determination of atrazine and its metabolites in target tissues and then use it to determine how atrazine¿s tissue disposition and pharmacokinetics are influenced by prior or concurrent dieldrin exposure. Our long-term goal is to understand better how the pharmacokinetics and tissue distribution of environmentally-relevant pesticides changes when organisms are exposed to pesticide mixtures. More specifically, we will determine whether prior/ongoing exposure to dieldrin will alter atrazine¿s pharmacokinetics. When completed, this research is expected to not only delineate the effects of dieldrin exposure on the pharmacokinetics of atrazine, but to also underscore the importance of pesticide interaction in risk assessment.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一，该子项目和研究者 (PI) 可能已从其他 NIH 来源获得主要资助，因此可以在其他 CRISP 机构中得到体现。所列出的内容是针对该中心的，该中心不一定是研究人员所在的机构。阿特拉津是美国广泛使用的除草剂之一，它对多种器官系统产生有害影响。这些研究、组织剂量测定和药代动力学研究与人类健康的相关性是必要的。此外，莠去津的代谢在很大程度上取决于细胞色素 P450 (CYP) 单加氧酶的活性，这些农药目前已被禁用，但仍广泛存在于体内。环境，例如杀虫剂狄氏剂，是已知的 CYP 诱导剂。狄氏剂的持久性和莠去津的大量使用，增加了同时接触这两种农药的可能性。分析生物基质中莠去津的分析方法有多种缺点。我们最近开发了一种 LC-MS 方法来分析小鼠血浆和尿液中的莠去津及其所有主要哺乳动物代谢物。在本项目中，我们将优化这种测定莠去津的方法。及其在靶组织中的代谢物，然后用它来确定莠去津如何？我们的长期目标是更好地了解当生物体接触农药混合物时，环境相关农药的药代动力学和组织分布如何变化。之前/持续接触狄氏剂会改变莠去津??完成后，这项研究预计不仅会描述狄氏剂暴露对莠去津药代动力学的影响，而且还会强调农药相互作用在风险评估中的重要性。