BIOMARKERS OF CHLOROETHENE(S) EXPOSURE AND EFFECT(S)

氯乙烯暴露的生物标志物及其影响

• 批准号: 2018785
• 负责人: GHULAM A.S. ANSARI
• 金额: $ 10.08万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-01-01 至 1998-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2018785
• 关键词: adduct; antibody; autoimmune disorder; binding proteins; bioassay; biomarker; disease /disorder model; disease /disorder proneness /risk; enzyme linked immunosorbent assay; haloalkene; immunotoxicity; laboratory mouse; method development; occupational hazard

DESCRIPTION: (Adapted from the Investigator's Abstract) Fatalities from work related injury or disease are on the decline, while nonfatal injuries or illnesses are increasing at an alarming rate. The U.S. Public Health Service targets a 22% reduction in such incidents by the year 2,000. In chemical industries most such illnesses result from exposure to toxic industrial chemicals; this problem can be ameliorated by minimizing the exposure and using sensitive surveillance procedures. This research seeks to develop newer and more sensitive methods to measure exposure and its effect(s). Occupational exposure to chloroethenes (also known as chloroethylenes) results in such immunological diseases/syndromes as scleroderma, systemic lupus erythematosus (SLE) and Goodpasture's Syndrome. Exposure to these chemicals becomes apparent only when adverse outcome or disease symptoms become evident, and irreversible damage has probably already occurred. Therefore, the focus of this demonstration project is to develop mechanistically based biological markers of exposure to chloroethenes. These compounds bind to proteins. The PI will use this property to develop methods to measure adduct(s) of chloroethene(s) with such circulatory protein(s) as hemoglobin and /or albumin. The covalently bound macromolecule can act as immunogen(s) and elicit the production of chloroethene-specific antibodies which will be quantitated by ELISA. The early detection of these chemical-specific antibodies can alert at-risk individuals to the potential of developing autoimmune disease(s), and therefore, will provide an early opportunity for intervention via preventive or therapeutic strategies. Autoimmunity-prone mice MRL +/+ will be used as animal models. The model compound, will be tetrachloroethane, which is used extensively in the dry cleaning industry, where a significant population is exposed to this chemical on a regular basis. The methods thus developed from their work should lead to new approaches for biomonitoring and medical surveillance of the occupationally exposed population, as well as for risk assessment.

描述：（改编自研究者摘要） 与工作有关的伤害或疾病正在下降，而非致命伤害 或者疾病正以惊人的速度增加 美国公共卫生 服务的目标是到2000年将此类事件减少22%。 在 大多数这类疾病是由于接触有毒物质而引起的。 工业化学品;这个问题可以通过最大限度地减少 曝光和使用敏感的监视程序。 这项研究旨在 开发更新和更灵敏的方法来测量暴露及其 影响 职业性接触氯乙烯（也称为氯乙烯） 导致免疫性疾病/综合征，如硬皮病、系统性 红斑狼疮（SLE）和肺出血肾炎综合征。 暴露于这些 化学物质只有在出现不良后果或疾病症状时才变得明显 很明显，不可逆转的损害可能已经发生。 因此，该示范项目的重点是开发 暴露于氯乙烯的机械生物标志物。 这些化合物与蛋白质结合。 PI将使用此属性开发 测量具有这种循环的氯乙烯加合物的方法 蛋白质如血红蛋白和/或白蛋白。 共价结合的 大分子可以作为免疫原，并引发免疫原的产生。 氯乙烯特异性抗体，其将通过ELISA定量。 的 这些化学特异性抗体的早期检测可以警告风险 个体患自身免疫性疾病的可能性，以及 因此，将提供通过预防性干预的早期机会， 或治疗策略。 自身免疫易感小鼠MRL +/+将用作 动物模型 模型化合物将是四氯乙烷， 广泛应用于干洗行业，在那里有大量的人口 经常接触这种化学物质 从他们的工作中发展出来的方法应导致新的办法， 职业接触者的生物监测和医学监测 人口，以及风险评估。