IMMUNOCHEMICAL METHODS TO MONITOR TOXIC SUBSTANCES IN HUMANS AND OTHER SPECIES

评估有害物质对人体构成的风险 环境，一个中心问题是分析。免疫分析发现他们的 在更成熟的有毒物质测量方法中 环境，并在人类监测中发挥主要作用。 免疫分析的优点包括分析速度快、成本效益高、 对多种化合物的敏感性、特异性、适用性和 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。三嗪除草剂是 良好的农业污染指标。这一检测方法的发展 一类化合物将继续我们的目标，如扑尔敏，2- 羟基、单脱烷基代谢物和双脱烷基代谢物 父母和代谢物的一组分析。2，3，7，8- 四氯二苯并二恶英是一种化合物，它对人类和 环境健康仍然是争论的主题，是一个很好的例子 分析成本极高的化合物。开发特定的 免疫分析对合成化学家来说将是一个挑战。在如铅中 和镉也成为了目标。污染程度甚至没有 由于样品制备方面的独特问题和 分析。 第二个目标是开发评估人类接触和 效果。这些化验方法的发展与理解密切相关 毒性的机理基础，也将为 探索这样的基本机制。与其他工人合作 本课程将探讨细胞毒性的标记物和机制。 具体提议的目标包括三嗪硫代碳酸酯(尿液 三嗪的代谢物)、硝基酚(某些工业产品的代谢物 中间体、炸药和有机磷杀虫剂)、萘 硫代巴比妥酸盐(尿中萘的代谢物)、松弛素(一种 隐匿性怀孕)和14K Clara细胞蛋白(靶标的一个例子 可能特别涉及细胞毒性的蛋白质)。 我们的第三个目标是开发新的免疫化学技术。 用于环境领域。技术将发展到 界面免疫分析与经典分析程序，如 利用抗体进行亲和分离和净化或作为检测器 在经典的清理之后(即超临界流体萃取)。使用 专家系统在实现免疫化学检测中的应用 将对环境化学进行评估。统计方面的考虑 分析最佳分析策略，低分析物浓度和 多分析问题将被开发出来。

For evaluating the risk posed by hazardous substances in humans and the environment, a central problem is analysis. 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. Assay development for this class of compounds will continue our targets such as prometon, the 2- hydroxy and mono and didealkylated metabolites in order to develop a battery of assays for parents and metabolites. 2,3,7,8- Tetrachlorodibenzodioxin is a compound whose impact in human and environmental health is still subject to debate and is a prime example of a compound for which analysis costs are extremely high. Developing specific immunoassays will be a challenge to the synthetic chemist. In such as lead and cadmium have also been targeted. Levels of contamination have not even begun to be addressed due to the unique problems in sample preparation and analysis. The second objective is to develop assays to assess human exposure and effect. Development of these assays is intimately tied to an understanding of the mechanistic basis of toxicity and also will provide new reagents for probing such fundamental mechanisms. In collaboration with other workers markers for and the mechanisms of cellular toxicity will be addressed. Specifically proposed targets include triazine mercapturates (urinary metabolites of triazines), nitrophenols (metabolites of some industrial intermediates, explosives and organophosphate insecticides), naphthalene mercapturate (urinary metabolites of naphthalene), relaxin (an indicator of occult pregnancy) and the 14K Clara cell protein (an example of a target protein that may be specifically involved in cellular toxicity). Our third objective is the development of new immunochemical technologies for use in the environmental field. Techniques will be developed to interface immunoassay with classical analytical procedures such as utilizing antibodies for affinity separation and cleanup or as detectors following classical cleanup (i.e. supercritical fluid extraction). Use of expert systems in the implementation of immunochemical detection into environmental chemistry will be evaluated. Statistical consideration for analysis of optimum assay strategies, low analyte concentration and multianalyte problems will be developed.