Manganese, Iron, Cadmium & Lead Transport from the Environment to Critical Organs

项目#3探索铁，锰，镉和铅从儿童经历的环境中运输到血液和关键器官，如大脑，心脏，肝脏和肾脏。我们试图更好地了解儿童和他们的母亲在焦油溪设置的金属暴露，通过（1）利用怀孕期间和怀孕后的暴露，（2）使用金属离子以及焦油溪复杂的环境样本，（3）比较不同的途径， 从环境进入身体。项目3还将探讨有毒金属和铁的作用，因为它们相互作用，影响金属的吸收。在动物模型中，我们将同时研究金属转运的分子机制以及金属从鼻，肺和肠道到血液，中枢神经系统和其他器官的相应药代动力学。这些数据将与两种动物的结局相关 （项目4）和人类研究（项目1）。当项目3的数据与项目2的暴露评估相结合时，我们将能够更好地确定哪些暴露途径导致最严重的有毒金属身体负担。从这方面的知识，我们应该能够制定最佳战略，在焦油溪，以减少有毒金属的剂量给母亲和儿童，从而更好地回应公民的环境问题，在焦油溪，俄克拉荷马州。

Project #3 explores the transport of iron, manganese, cadmium and lead from environments experienced by children to the blood and critical organs like the brain, heart, liver, and kidney. We seek to better understand metal exposures of children and their mothers in settings like Tar Creek by (1) utilizing exposures during and after pregnancy, (2) using metal ions as well as complex environmental samples from Tar Creek, and (3) comparing different routes of entry from the environment into the body. Project 3 will also explore the role of toxic metals and iron status as they interact to influence metal absorption. In animal models, we will simultaneously study both the molecular mechanisms of metal transport as well as the corresponding pharmacokinetics of metals from the nose, lung and gut to the blood, central nervous system, and other organs. These data will be correlated with outcomes in both animal (Project 4) and human studies (Project 1). When data from Project 3 are combined with exposure assessment in Project 2, we will be able to better identify which routes of exposure result in the most significant body burdens of toxic metals. From this knowledge, we should be able to craft optimal strategies in Tar Creek to reduce the dose of toxic metals to mothers and children and thus better respond to the environmental concerns of the citizens in Tar Creek, Oklahoma.