INTEGRATED CLINICAL & BASIC STUDIES OF HUMAN TOXICOLOGY

该项目由临床医生组成， 临床医生/科学家和基础科学家致力于 将所需的科学和临床资源结合在一起 直接在人体或人体组织中研究 环境中的有毒物质。这与标准的背离 环境毒理学研究的新途径 代理人的基础是认识到与人类的相关性 可以在动物体内或体外系统中建立毒性测试 只有通过在人类身上进行批判性实验或 人类来源的组织。在项目1中，特点和 纯化的人肝在人肝组织中的分布 患者体内的细胞色素P-450。项目3提议使用类似的 生物化学和分子生物学技术研究细菌 人肝组织醛固酮还原酶参与机体的代谢 有机氯农药，十氯酮。在项目4中，生物化学 并将使用细胞学探针来研究这种机制 有机磷对神经系统的毒性。在项目中 5.生物化学和微穿刺术将用于 研究金属对肾小球和肾小管损伤的机制。 项目6是临床研究的核心，由医学 专科(神经精神科、肺科、心血管科、 肝、肾、皮肤科、泌尿科、分析实验室) 能够评估特定器官的毒性。核心也是 由可供调查的患者群体组成。 这些人包括有记录的过度接触镉的工人和 有记录的环境过敏性皮炎患者 探员们。预计拟议的研究将提供新的 有关因以下原因引起的毒性的临床表现 环境代理人，洞察这些损害的机制 毒剂，以及对一些解毒的更好的理解 酶系统。此外，我们预计该计划将体现 临床医学在人类研究中的应用 毒物学。

This Program Project is comprised of Clinicians, Clinician/Scientists, and Basic Scientists working to bring together the scientific and clinical resources needed to investigate directly in humans or in human tissues the effects of toxic substances in the environment. This departure from standard approaches to investigation of the toxicology of environmental agents is based on the recognition that the relevance to man of toxicity testing in animals or in vitro systems can be established with certainty only by making critical experiments on humans or on human derived tissues. In Project #1 the characteristics and distribution among human liver samples of purified human liver cytochromes P-450 in patients. Project #3 proposes to use similar biochemical and molecular biologic techniques to investigate a human liver aldo-keto reductase involved in the metabolism of the organochlorine pesticide, chlordecone. In Project #4, biochemical and cytological probes will be used to investigate the mechanisms of toxicity of organophosphates on the nervous system. In Project #5, biochemical and micropuncture techniques will be used to examine mechanisms of glomerular vs. tubular injury by metals. Project #6 is the Clinical Research Core comprised of medical specialty units (neuro-psychiatric, pulmonary, cardiovascular, liver, renal, dermatology, urology, analytical laboratories) capable of evaluating organ specific toxicity. The Core also is comprised of patient populations available for investigation. These include workers with documented over-exposure to cadmium and patients with documented allergic dermatitis to environmental agents. The proposed studies are expected to provide new information about clinical manifestations of toxicity due to environmental agents, insight into the mechanism of injury by these agents, and a greater understanding of some detoxification of enzyme systems. Moreover, we expect this Program to exemplify the utility involving clinical medicine in the study of human toxicology.