Target Organ DNA Damage in Coke Oven Workers

焦炉工人靶器官 DNA 损伤

• 批准号: 7698722
• 负责人: Glenn Talaska
• 金额: $ 22.41万
• 依托单位: UNIVERSITY OF CINCINNATI
• 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 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7698722
• 关键词: Target; Organ; DNA; Damage; Coke

DESCRIPTION (provided by applicant): Making accurate exposure measurements for polycyclic aromatic hydrocarbons remains one of the most vexing problems facing the occupational health professional. These compounds generally have low acute toxicity, but several are recognized carcinogens. They have a low vapor pressure, but are adsorbed onto particulates and are readily absorbed through the skin. For these reasons, biological monitoring is being increasingly used to estimate exposure. The focus of this proposal is to estimate the levels of exposure and early effects of PAH exposure in a population of German coke oven workers. Recent PAH exposure will be estimated using measurements of 1- hydroxypyrene (1HP) in pre-and post-shift urine samples. Chronic exposure over the last 100 days will be estimated by measurement of the levels of carcinogen-DNA adducts in the workers' exfoliated urothelial cells as the urinary bladder has been shown to be one of the target organs of in other groups of PAH exposed workers. Levels of these markers will be related measurements of airborne PAH in vapor and particulate phases that have already been made by our collaborators. This study will also present us with a unique opportunity to validate- by comparison with 1HP levels measured by the traditional HPLC method- a new method we have developed to measure 1HP and its glucuronide directly in the urine samples. This work will make several important contributions to the field. This will be the first examination of multiple biomarkers in coke oven workers that includes measurement of carcinogen DNA adducts in a target organ. This will allow to understand the relationship between external dose, internal dose and effective dose in a way that can be used to develop biological exposure guidelines to prevent health impact, rather than on population background levels as is currently the case for 1HP measurements. By validating the real time probe method in this field study we will determine whether it is feasible to use a method that rapidly provides results and feedback to workers as well as being able for the first time to control accurately for any inter-individual differences in conjugation pathways that may have effected 1HP measurements in earlier studies. Public Health Relevance: This study will investigate whether workers in coke ovens have increased levels of metabolites related to exposure and increased DNA damage in cells in their urine. These data will be useful to establish and occupational exposure guidance value that will protect the health of these and other workers.

描述（由申请人提供）：对多环芳烃进行准确的暴露测量，仍然是职业卫生专业人员面临的最烦人的问题之一。这些化合物通常具有低急性毒性，但有几种是公认的致癌物。它们的蒸气压力低，但被吸附到颗粒上，并很容易通过皮肤吸收。由于这些原因，生物监测越来越多地用于估计暴露。该提案的重点是估计PAH暴露的暴露水平和在德国可乐工人人群中的暴露水平和早期影响。使用1-羟基苯乙烯（1HP）在换档前后的尿液样品中，将估计PAH暴露于最近的PAH暴露。在过去100天内的慢性暴露将通过测量工人的去角质尿路上皮细胞中的致癌物中加合物的水平来估计，因为尿膀胱已被证明是其他PAH暴露的工人中其他组的目标器官之一。这些标记的水平将是我们合作者已经进行的蒸气和颗粒相的空中PAH的相关测量。这项研究还将通过与传统的HPLC方法测量的1HP水平进行比较，为我们提供一个独特的机会，这是我们开发的一种新方法，可以直接在尿液样品中测量1HP及其其葡萄糖醛酸。这项工作将为该领域做出一些重要的贡献。这将是对可口烤箱工人中多个生物标志物的首次检查，其中包括测量目标器官中的致癌DNA加合物。这将使外部剂量，内剂量和有效剂量之间的关系以一种可用于制定生物暴露指南以防止健康影响的方式，而不是像目前对1HP测量的情况一样。通过验证本领域研究中的实时探测方法，我们将确定使用一种可以快速为工人提供结果和反馈的方法，并首次能够准确地控制与早期研究中1HP测量的共轭途径中的任何个体间差异。 公共卫生相关性：这项研究将调查可口烤箱中的工人是否具有与暴露相关的代谢产物水平增加，并且尿液中细胞中DNA损伤增加。这些数据将对建立和职业暴露指导价值有用，以保护这些和其他工人的健康。