Molecular Mechanisms

描述(由申请人提供)：儿童环境健康风险研究中心的总体重点是确定儿童对杀虫剂的易感性的机制。分子机制研究将具体评估农药发挥神经发育毒性的分子和细胞毒性机制。神经细胞增殖、分化和细胞死亡的调节动力学的变化将被检验。这些功能的后果将在神经行为评估设施核心中进行评估。这些研究将补充遗传易感性研究项目，在这些项目中，将研究遗传变异性对有机磷农药新陈代谢的影响。总体而言，这三项基于实验室的研究提供了体内和体外评估以及分子、细胞和遗传评估的最佳组合。这些实验室发现将直接适用于风险表征核心及其基于生物的剂量反应模型。来自暴露评估机制核心的信息将确保这些量化评估是现实的。

Description (provided by applicant): The overall focus of the Center for Child Environmental Health Risk Research is on mechanisms that define children's susceptibility to pesticides. The Molecular Mechanisms Study will specifically evaluate the molecular and cellular mechanisms of toxicity through which pesticides can exert their neurodevelopmental toxicity. Alterations in the regulatory dynamics of neural cell proliferation, differentiation, and cell death will be examined. The functional consequences of these will be assessed in the Neurobehavioral Assessment Facility Core. These studies will complement the Genetic Susceptibility Research Projects where the impacts of genetic variability in organophosphate pesticide metabolism will be examined. In total these three laboratory based studies provide an optimal mix of in vivo and in vitro assessments and molecular, cellular, and genetic evaluations. These laboratory findings will fit directly into the Risk Characterization Core and its biologically based dose response models. Information from the Exposure Assessment Facility Core will ensure that these quantitative assessments are realistic.