Superfund Basic Research Program at Boston University

描述(由申请人提供) 这一竞争性更新的科学主题延续了赠款申请中的主题：暴露于环境有害物质对人类和野生动物繁殖和发育的影响。特别强调由于废物处理管理不当而经常遇到的物质。正在研究的化学物质是有机物，既有卤化化合物，也有非卤化化合物。该方案将侧重于外来物质/内分泌相互作用的基本机制及其影响，以便更好地了解环境中有害物质扰乱生殖和发育过程的影响。9个项目(5个生物医学项目和4个非生物医学项目)将研究：1)饮用水中暴露于全氯乙烯(PCE，一种过氧化体增殖物)的人群神经发育的流行病学研究，以及研究类似环境问题的流行病学技术(2个生物医学项目)；2)基于受体的细胞内受体和信号通路在生物和组织发育中的作用研究(受体/途径：AH受体，AhR；过氧化体增殖物激活受体，PPAR；雌激素受体，ER；雄激素受体，AR；MAP激酶途径)重要的外源物质(平面卤代芳烃，PHAHs；多环芳烃，PAHs；和过氧物酶增殖物，特别是邻苯二甲酸盐)，以及3个生物医学项目；3)涉及受体(AHRS、PPAR和ER)和细胞色素P450(1个非生物医学项目和2个生物医学项目)的鱼类种群对PHAHs和外来雌激素的毒性和抵抗力机制；4)通过地下水和沉积物对来自超级基金地点的地表水中复杂混合物的生殖和发育影响(包括AhR和ER介导的影响)的机制基础研究(1非生物医学)；5)用于修复多种外来物质的非生物非血红素铁催化剂氧化脱氯机理，包括其他项目中正在研究的所有那些。

DESCRIPTION (provided by applicant) The scientific theme for this competitive renewal continues the theme from the grant submission: effects of exposures to environmentally hazardous substances on reproduction and development in humans and wildlife. Special emphasis is placed on substances commonly encountered as a result of improperly managed waste disposal. The chemicals under study are organics, both halogenated and nonhalogenated compounds. The program will focus on the underlying mechanics of xenobiotics/ endocrine interactions and their effects to allow a better understanding of the implications of perturbations of reproductive and developmental processes by hazardous substances in the environment. Nine projects (5 biomedical and 4 nonbiomedical) will study: 1) Epidemiologic studies of neurodevelopment of a population exposed to perchlorethylene (PCE, a peroxisome proliferators) in drinking water, and epidemiologic techniques to study similar environmental problems (two biomedical projects); 2) receptor based mechanistic studies of the role of intracellular receptors and signaling pathways in the development of organisms and tissues (receptors/pathway: Ah receptor, AhR; peroxisome proliferator activated receptor, PPAR; estrogen receptor, ER; androgen receptor, AR; MAP kinase pathway) for important xenobiotics (planar halogenated aromatic hydrocarbons, PHAHs; polycyclic aromatic hydrocarbons, PAHs; and peroxisome proliferators, especially phthalates), and three biomedical projects; 3) Mechanisms of toxicity and resistance of fish populations to PHAHs and xenoestrogens involving receptors (AhRs, PPARs, and ERs) and cytochrome P450s (1 non-biomedical project and 2 biomedical); 4) studies of the mechanistic basis for reproductive and developmental effects on observed wildlife (including those mediated by AhR and ER) exposed to a complex mixture in surface water from a Superfund Site via groundwater and sediment (1 non-biomedical); 5) Mechanisms of oxidative dechlorination by an abiotic non-heme iron catalyst for remediation of a wide variety of xenobiotics, including all those under study in other projects.