IMMUNOCHEMICAL METHODS TO MONITOR TOXIC SUBSTANCES IN HUMANS AND OTHER SPECIES

监测人类和其他物种有毒物质的免疫化学方法

• 批准号: 3840745
• 负责人: BRUCE D HAMMOCK
• 金额: --
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3840745
• 关键词: antibody; artificial intelligence; biomarker; cadmium; chelating agents; diagnosis design /evaluation; environmental contamination; environmental toxicology; enzyme linked immunosorbent assay; haptens; heavy metals; herbicides; human subject; immunologic assay /test; industrial waste; laboratory mouse; laboratory rabbit; lead; monoclonal antibody; naphthalenes; nitrophenol; organic chemicals; relaxin; triazines; urinalysis

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.

用于评估有害物质对人体构成的风险， 环境，一个核心问题是分析。 免疫分析发现， 在较成熟的有毒物质测量方法中， 环境，并在人类监测中发挥主导作用。 免疫测定的优点包括分析速度、成本效益， 灵敏度、特异性、对多种化合物的适用性， 适应实验室或现场情况。 这项建议有三个目标。 一是快速发展， 对有害物质和环境退化的廉价分析 产品. 缺乏此类测定影响现场评价并限制了 开发良好的地下水运动模型，人类暴露， 研究补救系统。 几个复合类已经被 在本提案中确定用于测定开发。 三嗪除草剂是 农业污染的良好指标。 为此开发测定方法 类化合物将继续我们的目标，如prometon，2- 羟基和单和二脱烷基代谢物，以开发一种 母体和代谢物的一系列测定。 2,3,7,8- 四氯二苯并二恶英是一种化合物， 环境健康仍然是一个有争议的问题，它是一个很好的例子， 分析成本极高的化合物。 制定具体 免疫分析将是对合成化学家的挑战。 如铅 和镉也是目标。 污染程度甚至没有 由于样品制备中的独特问题， 分析. 第二个目标是开发评估人类接触的测定方法， 效果 这些检测方法的发展与理解 的机制基础的毒性，也将提供新的试剂 探索这些基本机制。 与其他工人合作 细胞毒性的标志物和机制将被解决。 特别提出的目标包括三嗪硫醇盐（尿 三嗪的代谢物），硝基酚（一些工业 中间体、炸药和有机磷杀虫剂）、萘 巯基尿酸盐（萘的尿代谢产物），松弛素（ 隐性妊娠）和14 K Clara细胞蛋白（靶点的一个例子 可能特异性参与细胞毒性的蛋白质）。 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。 将开发技术， 接口免疫测定与经典分析程序， 利用抗体进行亲和分离和净化或作为检测器 在经典的净化（即超临界流体萃取）之后。 使用 专家系统在实施免疫化学检测， 将对环境化学进行评估。 统计考虑因素 分析最佳检测策略、低分析物浓度和 将开发多分析物问题。