Characterizing chemical exposures and their health effects in humans, remains a significant challenge. This is due in part to the difficulties related to capturing the complexity of exposures and their interaction with biological systems, and to the fact that markers that can help disentangle this complexity are often at trace levels. Improved tools providing greater analytical sensitivity, combined with more comprehensive screening, are needed to move this field of research forward. Our laboratory is focusing on developing state-of-the-art high-resolution mass spectrometry-based methods to characterize the exposome and determine how it may interact with cellular targets which play key roles in carcinogenesis. We have recently developed a neutral loss screening and relative quantitation strategy to characterize reactive carbonyls in biological fluids and a metabolic profiling method for the tobacco-specific carcinogen NNK. In parallel, we are working on establishing a DNA adductomic approach based on a data dependent-constant neutral loss-MS3 (DDA-CNL/MS3) methodology as a comprehensive screening method to characterize all covalent DNA modifications (DNA adducts), induced by various exposures. These methods are based on the use of high-field orbital trap instrumentation (Thermo Scientific Orbitrap Fusion) which is very well suited for the analysis of challenging low-abundance, high-complexity samples. A number of examples will be presented in which the integrated MS-based methods we are developing are aimed at generating new comprehensive tools for the characterization of exposures in humans and for the elucidation of their effects on DNA.

High resolution mass spectrometry-based approaches for the investigation of chemical carcinogenesis

2019 Fall National Meeting

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