IMMUNOCHEMICAL METHODS TO MONITOR TOXIC SUBSTANCES IN HUMANS AND OTHER SPECIES

评估危险物质构成的风险的一个中心问题 在人类和环境中，缺乏能够 在快速周转时间内处理大量样品负载。免疫分析是 在更成熟的测量方法中找到自己的位置 环境中的有毒物质，对人类具有主导作用 监控。免疫分析的优点是分析速度快，成本低。 有效性、敏感度、特异度、适用性 化合物的种类和对实验室或野外环境的适应性。 这项提议有三个目标。一是快速发展， 有害物质和环境退化的廉价检测方法 产品。缺乏这样的分析会影响现场评估，并限制 开发良好的地下水运动模型、人类暴露模型和 关于补救制度的研究。几个复合类已经被 在本提案中确定用于分析开发。三嗪类除草剂 是农业污染的良好指标。以前的化验 母体及代谢和环境分解产品的开发 将用于监测研究。拟除虫菊酯，虽然很低 哺乳动物毒性，对鱼类等其他非靶标生物有毒 和水生无脊椎动物。申请率低，导致非常低(但是 强效)残留物使这组化合物特别困难 去分析。2，3，7，8-四氯二苯并二恶英对人体和人体的影响 环境健康仍然是争论的主题，是一个最好的例子。 一种分析成本极高的化合物。在……里面 与其他研究人员合作，化验萘，以及 将开发硝基萘。重金属，如汞、铅 和铜也成为了攻击目标。 第二个目标是开发评估人类接触和 效果。这些分析将被用来探索其机制基础 毒性。与其他工作人员合作，为 细胞毒性的机制将被讨论。硫代三嗪 和对硝基苯酚(一些工业中间体的代谢物， 爆炸物和有机磷杀虫剂)的检测将继续 已验证。新提出的目标包括一种通用的检测方法 硫代硫酸酯作为接触亲电物质的标志，并与蛋白质结合 萘的种类(目标的例子可以是特定的 参与细胞毒性)。 我们的第三个目标是应用新的免疫化学技术。 到环境领域。第一批技术将与免疫分析相结合 使用经典的分析方法，如利用抗体 亲和力分离和清理。专家系统在技术中的应用 将对转会进行评估。要解决的统计问题 多分析问题将被开发出来。新的报告分子(如 近红外荧光团)，以提高敏感性和更强大的酶对 将对提高保质期和便携性进行评估。最后是培训 而支持其他研究人员使用免疫分析将是 与培训核心合作提供。

A central problem to evaluating the risk posed by hazardous substances in humans and the environment is a lack of analytical techniques that can handle large sample loads with rapid turn around time. Immunoassays are finding their place among more established methods for measurement of toxic materials in the environment and have a predominant role in human monitoring. Advantages of immunoassays include speed of analysis, cost- effectiveness, sensitivity, specificity, applicability to a wide variety of compounds and adaptability to laboratory or field situations. This proposal has three objectives. The first is to develop rapid, inexpensive assays for hazardous substances and environmental degradation products. Lack of such assays affects site evaluation and limits the development of good models for groundwater movement, human exposure, and research on remediation systems. Several compound classes have been identified for assay development in this proposal. Triazine herbicides are good indicators of agricultural contamination. Assays previously development for parent and metabolic and environmental breakdown products will be used in monitoring studies. The pyrethroids, although of low mammalian toxicity, are toxic to other nontarget organisms such as fish and aquatic invertebrates. Low application rates, lead to very low (but potent) residues making this group of compounds particularly difficult to analyze. The impact of 2,3,7,8-tetrachlorodibenzodioxin on human and environmental health is still subject to debate and is a prime example of a compound for which analysis costs are extremely high. In collaboration with other investigators, assays for naphthalene, and nitronaphthalene will be developed. Heavy metals such as mercury, lead and copper have also been targeted. The second objective is to develop assays to assess human exposure and effect. These assays will be used to probe the mechanistic basis of toxicity. In collaboration with other workers markers for, and the mechanisms of; cellular toxicity will be addressed. Triazine mercapturate and p-nitrophenol (metabolites of some industrial intermediates, explosives and organophosphate insecticides) assays will continue to be validated. Newly proposed targets include a general assay for mercapturates as a marker of exposure to electrophiles, and protein bound species of naphthalene (an example of a target that may be specifically involved in cellular toxicity). Our third objective is the application of new immunochemical technologies to environmental field. The first techniques will interface immunoassay with classical analytical procedures such as utilizing antibodies for affinity separation and cleanup. Use of expert systems in technology transfer will be evaluated. Statistical considerations to address multianalyte problems will be developed. New reporter molecules (such as near IR fluorophores) to improve sensitivity and more robust enzymes to improve shelf life and portability will be evaluated. Finally training and support of other investigators in the use of immunoassay will be provided in collaboration with the Training Core.