Receptor-based developmental and reproductive toxicity of Superfund chemicals

波士顿大学超级基金研究中心的科学主题是超级基金化学品对人类和野生动物发育和繁殖的基于受体的毒性效应。正在研究的化学物质是SRP中心特别感兴趣的有机化合物，它们通过与细胞内称为受体的特定分子相互作用来启动毒性作用。这种相互作用启动了一系列事件，这些事件通常导致产生新的蛋白质，从而改变细胞的发育。研究范围从基本的实验室调查到通过饮用水或超级基金场地周围暴露的人群的大规模流行病学研究，或受污染港口鱼类生态的分子研究。其目的是更好地了解由于接触环境中的有害物质而对生殖和发育过程，包括衰老过程造成的影响。 一个特点是一套协调的平行项目，检查分子和人口的影响，在标准实验室斑马鱼模型和广泛的环境哨兵，鳉发育毒素。对接触高流行率的超级基金化学品四氯乙烯、多氯联苯、农药甲氧滴滴涕、邻苯二甲酸酯、有机锡和金属所产生的发育结果进行流行病学研究，目标是环保署/有毒物质和疾病登记署确定为特殊研究需要的知识空白。一个主要特点是开发新的方法来解决一些最困难的问题与典型的危险废物流行病学和毒理学数据集，时空分布和相互作用的混合物。研究支持核心为下一代测序的高度复杂的数据分析和分子结构的计算机建模提供专业知识，七个研究项目中有五个使用了这些技术。该中心包括两个核心设施，致力于将研究成果用于州和联邦机构的风险评估，并让公众和地方卫生当局参与制定和塑造科学研究议程。

The scientific theme for the Superfund Research Center at Boston University is receptor-based toxic effects of Superfund chemicals on development and reproduction in humans and wildlife. The chemicals under study are organic compounds of special interest to the SRP Center mandate that initiate their toxic actions by interacting with specific molecules inside cells called receptors. This interaction sets in motion chain of events that often leads to production of new proteins that alter the development of the cells. The research ranges from basic laboratory investigations to large scale epidemiologic studies of populations exposed through drinking water or around a Superfund site or molecular studies of fish ecology in a contaminated harbor. The object is to gain a better understanding of the implications of disturbances of reproductive and developmental processes, including aging, from exposures to hazardous substances in the environment. A special feature is a coordinated set of parallel projects examining molecular and population effects of developmental toxins in the standard laboratory zebra fish model and a widespread environmental sentinel, the killifish. Epidemiological studies of developmental outcomes from exposure to the high-prevalence Superfund chemicals perchloroethylene (PCE, tetrachloroethene), PCBs, the pesticide methoxychlor, phthalate, organotins and metals target knowledge gaps identified as special research needs by EPA/Agency for Toxic Substances and Disease Registry (ATSDR). A major feature is development of novel methods to address some of the most difficult problems associated with the typical hazardous waste epidemiological and toxicological datasets, temporal spatial distribution and interaction in mixtures. A Research Support Core provides expertise for highly sophisticated data analysis of Next Generation Sequencing and computer modeling of molecular structures, techniques used by five of the seven research projects. The Center includes two Core facilities dedicated to translating research for use in risk assessment by state and federal agencies and engaging the public and local health authorities in framing and shaping the scientific research agenda.