Innovations to Inform Occupational Disease Etiology Using Biomonitoring Methods

利用生物监测方法了解职业病病因的创新

• 批准号: 7672971
• 负责人: Jo Anna M. Shimek
• 金额: $ 3.77万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7672971
• 关键词: Innovations; Inform; Occupational; Disease; Etiology

DESCRIPTION (provided by applicant): Occupational disease etiology has been difficult to define due to the potentially long latency period between exposure to the harmful chemicals in workplace environment and the clinical manifestation of disease. While we typically monitor the air in the workplace for the presence of hazardous chemicals, we usually monitor for only one of these chemicals at a time and fail to evaluate the synergistic effects of chemical mixtures. Our ability to measure the presence of chemical contaminants in the body using biomonitoring technology continues to progress at a rapid pace, often before we clearly understand the meaning of the results. Our research group has identified a group of over 40 chemicals classified as known or suspected animal neurocarcinogens. By comparing our list to the National Occupational Exposure Survey (NOES) completed by the National Institute for Occupational Safety and Health (NIOSH) we have examined exposure to 24 chemicals from our list that are found in the workplace. We hypothesize that through the use of self-reported work histories an algorithm can be created to quantify cumulative occupational exposures to known or suspected animal neurocarcinogens. We further hypothesize that when cases and controls are compared there may be a statistically significant difference between the cumulative exposure scores of the two groups. Additionally, we hypothesize that hemoglobin adducts of 1, 3-butadiene and acrylamide are valid biomarkers of exposure and can be used to validate the exposure scoring method. Finally, we hypothesize that, by employing a mutagen sensitivity assay, a versatile method for evaluating DNA damage and repair capacity; we will be able to identify an interaction between environmental exposures, as measured by the relative exposure scores, and a genetic susceptibility to the damage caused by certain chemicals. From the results of this proposal, additional hypotheses may be generated to study specific industries and occupations. This research proposal will examine the work histories of study participants who have already participated in a brain cancer case-control study. Participants completed an extensive questionnaire and work history at the time of enrollment in the original study. From the work histories, a relative cumulative exposure score will be generated which evaluates exposure history to the 24 chemicals referenced above. The relative exposure scores will be compared between cases and controls with consideration made for various effect modifiers. Using these relative scores, a sub-set of the study control population will be identified to compare potential workplace exposures in their current occupation with hemoglobin adducts to two common chemicals, acrylamide and 1, 3-butadiene, which act as biomarkers of exposure. Laboratory analysis results will be correlated with the relative scores as a means of validating the scoring method. Finally, a biomarker of susceptibility will be analyzed using a mutagen sensitivity assay for these compounds, and results will be correlated with the relative cumulative exposure scores.

描述（由申请人提供）：由于在工作场所环境中接触有害化学品与疾病的临床表现之间可能存在较长的潜伏期，因此难以确定职业病的病因。虽然我们通常监测工作场所空气中是否存在危险化学品，但我们通常一次只监测其中一种化学品，无法评估化学混合物的协同效应。我们使用生物监测技术测量体内化学污染物存在的能力继续快速发展，通常在我们清楚地理解结果的含义之前。我们的研究小组已经确定了一组40多种化学物质被列为已知或疑似动物神经致癌物。通过将我们的清单与国家职业安全与健康研究所（NIOSH）完成的国家职业暴露调查（NOES）进行比较，我们检查了工作场所中发现的24种化学品的暴露情况。我们假设，通过使用自我报告的工作历史，可以创建一个算法来量化已知或疑似动物神经致癌物的累积职业暴露。我们进一步假设，当病例组和对照组进行比较时，两组的累积暴露评分之间可能存在统计学显著差异。此外，我们假设血红蛋白加合物的1，3-丁二烯和丙烯酰胺是有效的生物标志物的暴露，并可用于验证暴露评分方法。最后，我们假设，通过采用诱变剂敏感性试验，一个通用的方法，用于评估DNA损伤和修复能力，我们将能够确定环境暴露之间的相互作用，如测量的相对暴露分数，和遗传易感性的某些化学物质造成的损害。从这一建议的结果，额外的假设可能会产生研究特定的行业和职业。这项研究计划将检查已经参加脑癌病例对照研究的研究参与者的工作历史。参与者在最初的研究中登记时完成了广泛的问卷调查和工作历史。根据工作历史，将生成相对累积暴露评分，以评价上述24种化学品的暴露历史。将比较病例和对照组之间的相对暴露评分，并考虑各种效应修饰因子。使用这些相对评分，将确定研究对照人群的一个子集，以比较其当前职业中的潜在工作场所暴露与血红蛋白加合物对两种常见化学品丙烯酰胺和1，3-丁二烯的暴露，这两种化学品作为暴露的生物标志物。实验室分析结果将与相对评分相关联，作为验证评分方法的一种手段。最后，将使用这些化合物的诱变剂敏感性试验分析敏感性生物标志物，并将结果与相对累积暴露评分相关联。