AQUATIC BIOMARKERS IN SITE CHARACTERIZATION AND REMEDIATION

使用水生物种的脊椎动物活体模型将增强检测 与有毒废物场地相关的潜在健康危害自 污染物的扩散可能以地下水渗滤液、颗粒物 排放和地表水径流。这样做的总体目标是 研究是将传统的水生毒性方法与 建立反应生物标志物的最新方法学 复杂废物混合物的有毒成分。检测将包括终点 具有致突变性、致癌性和发育毒性。 鱼是被证实的环境哨兵和在这个实验室的研究 已经建立了青竹，一种小型水族馆硬骨鱼 鱼类作为首次筛选化学物质毒性的体内模型-- 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、速度和对新鲜、咸水和近岸的适应能力 海洋盐度可以对特定地点的条件进行建模。存在 小的，青竹允许对所有目标器官进行组织病理学采样 一次并通过使用大数字来提高统计精度，以及 启用全面采样以进行体视学评估。这个型号是 特别适合以毒性为基础的方法 站点的特征、站点内的区域设置的优先顺序、 生物修复的监测和有毒化合物的鉴定。使用 特定生命阶段的进一步表征了寄主的反应； 透明绒毛膜能够对发育进行非侵入性评估 工艺，脱铬确保准确的曝光时间和 敏感性、雏鸡急性毒性试验是首选和检测效果 接触对正常和异常(肿瘤形成)生长的影响。要实现 总体目标，提出了4个具体目标：1)测定遗传毒性 包括其特定沉淀物提取物的肝癌致癌性 河口和沿海生境，特别是军事基地附近的生境 在加利福尼亚州；2)对复杂混合物进行毒性测试，以及 有毒组分，使用快速IAA、高效液相色谱和气相色谱-质谱法进行鉴定 有毒成分；3)使用在噬菌体中制备的青竹cDNA文库， 筛查特定癌基因(Ras)和抑癌基因(P53)突变 以及特定酶的上调和/或下调调节，这些特定酶 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获得到县、州和联邦 为他们提供自我监控所需的工具和技能的员工 特定的站点。

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.