AQUATIC BIOMARKERS IN SITE CHARACTERIZATION AND REMEDIATION

使用水生物种的脊椎动物体内模型将增强检测 与有毒废物场地有关的潜在健康危害， 污染物的扩散可能发生在地下水沥滤物、颗粒 排放和地表水径流。本报告的总体目标 研究是将传统的水生毒性方法与 用于建立对以下的应答的生物标志物的现有技术方法 复杂废物混合物的有毒成分。试验将包括终点 致突变性、致癌性和发育毒性。 鱼类被证明是环境的哨兵，本实验室的研究 已经建立了青鳉（Oryzias latipes），一种小型水族馆硬骨鱼 鱼，作为体内模型，用于首次筛选化学品的毒性， 从有毒废物的土壤、水和空气中分离出的污染物混合物 网站.经济性、速度和对淡水、半咸水和近岸海岸的适应性 海洋盐度使得能够模拟特定地点的条件。被 小青鳉允许所有靶器官组织病理学取样， 一次，通过使用大量数据提高统计精度， 能够进行体视学评估的全面采样。该模型 特别适用于基于毒性的方法， 站点的特征描述，站点内区域设置的优先级， 监测生物修复和鉴定有毒化合物。使用 进一步表征了宿主的反应; 透明的绒毛膜可以无创地评估发育 工艺中，脱氯可确保准确的曝光时间， 敏感性，孵化急性毒性试验是第一次和检测效果 暴露对正常和异常（肿瘤发生）生长的影响。实现 总体目标，提出了4个具体目标：1）确定遗传毒性 包括特定沉积物提取物的肝癌性， 河口和沿海栖息地，特别是军事基地附近的栖息地 在加州; 2）对复杂混合物进行毒性分析， 毒性组分，使用快速IAA，然后用HPLC和GLC MS鉴定 毒性成分; 3）使用青鳉cDNA文库，在噬菌粒中制备， 筛选特异性癌基因（ras）和抑癌基因（p53）突变 以及用于特定酶的上调和/或下调， 对有毒化合物的反应指标;以及4）转让技术 从超级基金基础研究到县，州和联邦 员工为他们提供自我监控所需的工具和技能 具体网站。

Vertebrate in vivo models using aquatic species will enhance detection of potential health hazards associated with toxic waste sites since spread of contaminants may occur as ground water leachates, particulate emissions and surface water runoff. The overall objective of this research is to integrate conventional aquatic toxicity approaches with state of the art methodologies to establish biomarkers of response to toxic components of complex waste mixtures. Assays will include endpoints of mutagenicity, carcinogenicity, and developmental toxicity. Fish are proven environmental sentinels and studies in this laboratory have established the medaka (Oryzias latipes), a small aquarium teleost fish, as an in vivo model for first screening toxicity of chemical- contaminant mixtures isolated from soil, water and air at toxic waste sites. Economy, speed, and adaptability to fresh, brackish and near shore marine salinities enable modeling of site-specific conditions. Being small, medaka permit histopathologic sampling of all target organs at once and increase statistical precision through use of large numbers, and enable thorough sampling for stereologic assessment. This model is particularly well adapted for a toxicity-based approach to characterization of sites, prioritization of locales within a site, monitoring of bioremediation, and identification of toxic compounds. Use of specific life stages further characterizes host response; the transparent chorion enables noninvasive assessment of developmental processes, dechorionation ensures accurate timing of exposure and sensitivity, hatchling acute toxicity tests are first and detect effects of exposure on normal and abnormal (tumorigenesis) growth. To achieve the overall goal, 4 specific aims are proposed: 1) determine genotoxicity including hepatocarcinogenicity of specific sediment extracts from estuarine and coastal habitats, particularly those near military bases in California; 2) conduct toxicity assays on complex mixtures and, on toxic fractions, use rapid IAA followed by HPLC and GLC MS to identify toxic components; 3) use the medaka cDNA library, prepared in a phagemid, to screen for specific oncogene (ras) and suppressor gene (p53) mutations as well as for up and/or down regulations of specific enzymes which are indicators of response to toxic compounds; and 4) transfer technology obtained from superfund basic research to county, state and federal employees providing them with the tools and skills needed to self monitor specific sites.