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BIOMARKERS OF DIESEL EXHAUST PARTICLES
Impact/Purpose:
Specifically, this work will support efforts to (1) describe long-term health effects of particulate matter (PM) and co-pollutants in humans; (2) Validate utility of field-collected diesel exposure biomarkers; (3) Identify toxic source based components to be assessed for dose response studies; (4) Define PM toxicity by source derivation using in vivo and in vitro bioassay systems.
Description:
The objective of this project is to examine the detectability of some chemical components of diesel exhaust particles (DEP) in human urine following controlled human diesel exposures (IRB-approved). Ultimately, and upon validation, we propose to apply these components as biomarkers of DEP exposure in field studies. We will focus on identification of specific DEP biomarkers in urine because sampling is noninvasive; however biomarkers in other tissue compartments (eg, breath, blood) will also be assessed in the controlled exposures as an integral part of the method validation. Urinary DEP parent compounds and metabolites will be characterized as will DNA markers as measured in excreted urothelial cells. To accomplish these objectives, we will 1) examine the bioavailability of some chemical constituents of DEP after DEP incubation with biological fluids with and without cells, as cells may affect the "leaching" from DEP and metabolism of DEP components. Putative specific DEP markers (hopanes and long chain saturated alkanes) and more abundant components (i.e., recently characterized nitrophenols) will be measured; 2) determine optimal sampling time(s) for markers in urine based on an acute inhalation exposure to diesel exhaust. Subjects exposed to concentrated Chapel Hill PM can also provide samples for method validation. If an acute exposure does not produce detectable biomarkers, then subjects repeatedly exposed to fairly high concentrations of diesel exhaust (i.e., occupational exposures, school bus) can be examined. The biomarkers of DEP exposure will ultimately be used in appropriately designed field studies examining subjects exposed to ambient PM to determine the relationships between diesel derived markers and other parallel health effects measurements (e.g., heart irregularities, hospitalizations for asthma and lung infections, possibly lung cancer).