Humans are constantly exposed to mixtures, such as exhaust from diesel, gasoline and bio-fuels, containing several thousand compounds, including many known human carcinogens. Understanding health effects of exposure to mixtures is a daunting task and requires accurate characterization of the exposure and understanding of potential compound interaction. The main approach is to monitor as many potentially hazardous constituents as possible in air and water. However, it is well recognized that it will be a huge if not impossible undertaking to fully characterize complex exposures that constantly change and vary significantly between individuals and time. Therefore, internal biomonitoring such as metabolite profiling in urine and blood are considered to be more relevant since they represent actual absorbed constituents. To increase selectivity, analysis of DNA and protein adduct profiles have been proposed as most suitable because covalent binding to DNA and formation of stable adducts is believed to be the causal link between exposure and carcinogenesis. Most importantly, DNA and protein adducts retain sufficient chemical and structural information to ascertain individual compounds and are well established biomarkers for the internal dose. In this presentation we will outline current approaches and discuss advantages and limitations of technologies currently under development. We will present our latest results using hemoglobin adduct profiles as biomarkers for exposure to various mixtures.

Exposure profiling of potentially genotoxic constituents in complex mixtures such as vehicle exhausts

246th National Meeting (2013)

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