Diesel Exhaust: Biomarkers for Exposure

Diesel fuel exhaust is an extremely complex mixture of gasses and particles that undergo rapid chemical and structural changes after emission. When the exhaust is breathed in by dock workers, toll booth collectors, children in school busses, and the many others subjected to this exposure, diesel exhaust components enter the lungs. In efforts to quantify the amount of exposure a person has experienced, biomarkers can be analyzed. A biomarker is defined as any substance, structure or process that can be measured in a human as a result of exposure (W. A. Toscano Jr., PhD, Lecture 11/07/02). In the case of diesel fuel exhaust, there is no definite, accurate and specific biomarker. Research thus far has focused mainly on the measurement of DPM (diesel particulate matter) present in the atmosphere of occupational settings such as mines and highways, and not the measurement of levels within humans. This year, however, has brought some developments in research, and a trustworthy biomarker for exposure may be on the horizon.

Previously, biomarkers for DPM exposure has concentrated on the presence of polycyclic aromatic hydrocarbon (PAH) metabolites in urine. It was found, however, that this metabolite (1-hydroxypyrene) was present in significant levels only in cases of extremely high exposures. In an effort to improve the sensitivity of a biomarker, researchers in Japan found that the cytochrome P450 1A1 gene was expressed more frequently in rats exposed to DPM. (Takano et al. 2002) This gene appears to be induced in a dose dependant manner by a combination of PAH and dioxin, both of which are found in DE. This gene expression accelerates the production of reactive oxygen species (ROS) which are a key factor in the damage of lungs. By dissecting lung tissue and preparing PCR and a western blot analysis, the protein expression of Cyp 1A1 was quantified. This experiment was only a first step in analysis of Cyp 1A1 expression, and the feasibility and usefulness of this biomarker in humans is yet to be determined. As with many components of DPM, smoking among subjects is a significant confounder.
The polycyclic aromatic hydrocarbons induce not only Cyp 1A1 expression, but IgE production as well. The use of IgE as a biomarker for exposure was examined by researchers earlier this year, however, their results were not significant due to the fact that IgE levels are influence by many other factors other than DPM (Mastrangelo et al, 2002).

In conclusion, the accurate measurement of DE exposure in humans is currently not feasible. In order for an ideal biomarker to be discovered, it is necessary for researchers to fully understand the components of DE as well as the physiology of how the diesel exhaust particles interact and disperse in the human body.

For more information:

Giuseppe et al., 2002. Exposure to diesel exhaust enhances total IgE in non-atopic dockers. International Archives of Occupational and Environmental Health. Published online 11-September-2002.

Takano et al., 2002. Lung expression of cytochrome P450 1A1 as a possible biomarker of exposure to diesel exhaust particles. Archives of Toxicology. 76: 146-155.