Target Organ DNA Damage in Coke Oven Workers

University Of Cincinnati, Cincinnati OH

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Abstract

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.