Superfund Basic Research Program at Boston University

描述（由申请人提供） 本次竞争性更新的科学主题延续了资助申请的主题：暴露于有害环境物质对人类和野生动物生殖和发育的影响。特别强调由于废物处置管理不当而经常遇到的物质。正在研究的化学品是有机物，包括卤化和非卤化化合物。该计划将侧重于外源性物质/内分泌相互作用及其影响的基本机制，以便更好地了解环境中有害物质对生殖和发育过程的干扰的影响。九个项目（5个生物医学和4个非生物医学）将研究：1）接触过氯乙烯人群神经发育的流行病学研究（PCE，过氧化物酶体增殖物）在饮用水中的含量，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）以受体为基础的机制研究细胞内受体和信号通路在生物体和组织发育中的作用（受体/途径：Ah受体，AhR;过氧化物酶体增殖物激活受体，PPAR;雌激素受体，ER;雄激素受体，AR; MAP激酶途径）（平面卤代芳烃、多环芳烃和过氧化物酶体增殖剂，特别是邻苯二甲酸酯），以及三个生物医学项目; 3）鱼类种群对PHAH和涉及受体的外源雌激素的毒性和抗性机制（AhRs、PPARs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）; 4）研究对所观察到的野生动物的生殖和发育影响的机制基础（包括AhR和ER介导的那些）通过地下水和沉积物暴露于来自超级基金场地的地表水中的复杂混合物（1个非生物医学）; 5）非生物非血红素铁催化剂氧化脱氯的机制，用于补救各种各样的外源性物质，包括其他项目正在研究的所有外源性物质。

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.