INTEGRATED CLINICAL & BASIC STUDIES OF HUMAN TOXICOLOGY

该计划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 整合所需的科学和临床资源， 直接在人体或人体组织中研究 环境中的有毒物质。 这种背离标准的做法 环境毒物毒理学研究方法 代理人是基于这样的认识，即与人的相关性， 可以建立动物或体外系统中的毒性测试 只有通过对人类或其他动物进行批判性实验， 人源组织。 在项目#1中， 纯化人肝的人肝样品中的分布 患者的细胞色素P-450。 项目#3建议使用类似的 生物化学和分子生物学技术， 人肝醛酮还原酶参与的代谢 有机氯农药，十氯酮。 在项目#4中，生物化学 细胞学探针将用于研究其机制 有机磷对神经系统的毒性。 在项目 #5，生化和微穿刺技术将用于 研究金属对肾小球和肾小管损伤的机制。 项目#6是临床研究核心，包括医学 专业单位（神经精神，肺，心血管， 肝脏、肾脏、皮肤科、泌尿科、分析实验室） 能够评估器官特异性毒性。 核心也是 包括可用于研究的患者人群。 这些人包括有文件证明的过度接触镉的工人， 有记录的环境过敏性皮炎患者 剂. 预计这些研究将提供新的 关于由以下原因引起的毒性的临床表现的信息 环境因素，深入了解这些因素的伤害机制 代理商，和一些解毒的更大的了解， 酶系统 此外，我们预计该计划将使 临床医学在人类研究中的应用 毒理学

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.