OCCUPATIONAL NEUROPATHIES DUE TO INDUSTRIAL CHEMICALS

工业化学品引起的职业性神经病

• 批准号: 3420060
• 负责人: MOHAMED B ABOU DONIA
• 金额: $ 19.7万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3420060
• 关键词: SDS polyacrylamide gel electrophoresis; aminoacid; autoimmune disorder; autoradiography; biomarker; cell mediated cytotoxicity; chickens; crosslink; cytochrome P450; cytoskeletal proteins; environmental toxicology; enzyme linked immunosorbent assay; haptens; histopathology; hydrocarbons; immunocytochemistry; ketones; laboratory mouse; laboratory rat; lymphocyte; messenger RNA; microtubule associated protein; monoclonal antibody; nervous system disorder; neural degeneration; neurofilament; neurotoxins; occupational disease /disorder; organophosphorus insecticide; phosphoproteins; synthetic nucleic acid; toxicant interaction; toxicology; western blottings

The goal of this proposal is to continue studying the mechanism(s) and develop specific markers of the neurotoxic action resulting from exposure to neurotoxic chemicals, a situation that is frequently encountered in industry (1). We will continue studying the mechanism of the joint neurotoxic action of EPN and aliphatic hexacarbons at the neurotoxicity target, the brain and spinal cord. We will also carry out studies to develop a clinical marker, by producing monoclonal antibodies to these specific neurotoxicants, for detecting and testing for exposure of workers to these chemicals. We will divide the proposal into four major sections, although there will be significant overlap in the studies in each of these sections. 1. Development of specific monoclonal antibodies to neurotoxic chemicals. 2. Study the mechanism of action of CS2 and hexacarbon induced neurotoxicities. 3. Study the relationship of the immune system to the development of neurotoxicity. 4. Continue work on the mechanism of interaction of aliphatic hexacarbons and EPN on the brain and spinal cord. In the first section we will investigate the development of monoclonal antibodies to specific neurotoxic chemicals. These antibodies would be chemical specific and would recognize protein bound neurotoxicant, independent of which protein the compound in bound. These antibodies would therefore be useful in the clinical diagnosis of exposure to these compounds. The second section will focus on the mechanism of action of these compounds on the nervous system. Since CS2 and hexacarbons produce nearly identical pathologies we will investigate if there is a common mechanism of action of these two classes of compounds. In the third section, we will investigate the possible role of the immune system on nerve degeneration that is observed after exposure to the chemicals which can covalently modify proteins, thus creating a hapten or foreign substance which is then recognized by the immune system. In the final section we continue work on the joint mechanism of action of organophosphorus compounds and hexacarbon compounds. In this work will focus on the role of cytochrome P-450 in the nervous system on the joint mechanism of action of these compounds.

该提案的目标是继续研究机制和 开发暴露引起的神经毒性作用的特定标记 神经毒性化学物质，这种情况经常遇到 工业 (1). 我们将继续研究联合机制 EPN 和脂肪族六碳化合物的神经毒性作用 目标，大脑和脊髓。 我们还将开展研究 通过生产针对这些的单克隆抗体来开发临床标志物 特定的神经毒物，用于检测和测试工人的暴露情况 对这些化学品。 我们将提案分为四个主要部分， 尽管这些研究中的每一个都会有很大的重叠 部分。 1. 神经毒性化学物质特异性单克隆抗体的开发。 2.研究CS2和六碳诱导的作用机制 神经毒性。 3. 研究免疫系统与发育的关系 神经毒性。 4. 继续研究脂肪族六碳化合物的相互作用机制 和 EPN 对大脑和脊髓的影响。 在第一部分中，我们将研究单克隆抗体的发展 针对特定神经毒性化学物质的抗体。 这些抗体将是 化学特异性并能识别蛋白质结合的神经毒物， 与化合物结合的蛋白质无关。 这些抗体会 因此可用于暴露于这些物质的临床诊断 化合物。 第二部分将重点介绍其作用机制 这些化合物对神经系统。 由于 CS2 和六碳化合物会产生 几乎相同的病理学，我们将调查是否存在共同点 这两类化合物的作用机制。 在第三个 部分，我们将研究免疫系统的可能作用 接触化学物质后观察到的神经变性 可以共价修饰蛋白质，从而产生半抗原或外来物质 然后被免疫系统识别。 在最后一节我们 继续研究有机磷的联合作用机制 化合物和六碳化合物。 在这项工作中，我们将重点关注以下角色： 细胞色素P-450在神经系统关节中的作用机制 这些化合物。