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

描述：(改编自《调查员摘要》) 与工作有关的伤害或疾病在减少，而非致命的伤害 或者，疾病正在以惊人的速度增加。美国公共卫生 服务的目标是到2000年将这类事件减少22%。在……里面 化学工业大多数此类疾病是由接触有毒物质引起的 工业化学品；这个问题可以通过最小化 暴露和使用敏感的监视程序。这项研究寻求 开发新的、更灵敏的方法来测量暴露和其 效果(S)。 职业接触氯乙烯(也称为氯乙烯) 导致系统性硬皮病等免疫性疾病/综合征 红斑狼疮(SLE)和古德帕斯普雷综合征。暴露在这些环境中 只有当不良后果或疾病症状出现时，化学品才会变得明显 显而易见，不可逆转的损害很可能已经发生了。 因此，这个示范项目的重点是开发 接触氯乙烯的机械生物标记物。 这些化合物与蛋白质结合。PI将使用此属性来开发 用这种循环测定氯乙烯加合物(S)的方法 蛋白质(S)，如血红蛋白和/或白蛋白。共价结合 大分子可作为免疫原(S)并诱导产生 将通过酶联免疫吸附试验进行定量的氯乙烯特异性抗体。这个 及早检测到这些化学特异性抗体可以提醒高危人群 个体可能罹患自身免疫性疾病(S)，以及 因此，将提供通过预防性干预的早期机会 或治疗策略。具有自身免疫倾向的小鼠MRL+/+将用作 动物模型。模型化合物将是四氯乙烷，它被用于 广泛应用于干洗业，那里有相当大的人口 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该会导致新的方法 职业性接触者的生物监测和医学监护 人口数量，以及风险评估。

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.