IMMUNOCHEMICAL METHODS TO MONITOR TOXIC SUBSTANCES IN HUMANS AND OTHER SPECIES

评估危险物质风险的一个核心问题 在人类和环境中，缺乏分析技术， 处理大量样品负载，周转时间短。免疫测定是 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，并在人类 监测.免疫测定的优点包括分析速度、成本- 有效性、灵敏度、特异性、适用性 化合物和实验室或现场情况的适应性。 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。三嗪类除草剂 是农业污染的良好指标。先前的分析 母体和代谢及环境分解产物的开发 将用于监测研究。虽然除虫菊酯含量低， 对哺乳动物的毒性，对其他非目标生物如鱼类有毒 和水生无脊椎动物。施用率低，导致非常低（但 有效的）残基使得这组化合物特别难以 来分析。2，3，7，8-四氯二苯并二恶英对人体及 环境健康仍然是争论的主题， 分析成本极高的化合物。在 与其他研究人员合作，测定萘， 将开发硝基萘。重金属如汞、铅 和铜也成为了目标。 第二个目标是开发评估人类接触的测定方法， 效果这些试验将用于探索 毒性与其他工人合作， 的机制;细胞毒性将得到解决。三嗪巯基尿酸盐 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）检测将继续进行 验证.新提出的目标包括一个通用的分析， 巯基尿酸盐作为暴露于亲电试剂的标志物， 萘的种类（可以具体地 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。第一种技术将免疫分析 使用经典的分析方法，例如利用抗体 亲和分离和净化。专家系统在技术中的应用 转让将被评估。需要解决的统计问题 将开发多分析物问题。新的报告分子（如 近红外荧光团），以提高灵敏度和更强大的酶， 将评价改进保存期限和便携性。最后训练 并支持其他研究者使用免疫测定法， 与培训中心合作提供。

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.