Characterizing chemical exposures in humans remains a significant challenge. Our lab has been developing state-of-the-art high-resolution mass spectrometry-based methods to characterize the exposome and determine how it may influence overall health. Because it is challenging to capture the complexity of exposures, often at trace levels, improved tools are needed to move this field of research forward. We have recently developed a neutral loss (NL) screening and relative quantitation strategy for the targeted analysis of reactive carbonyls in biological fluids. In addition, a comprehensive DNA adductomics approach was developed to characterize covalent modifications in DNA generated from these exposures. Here, we have integrated these MS-based methods to characterize electronic cigarette exposure in humans, with the goal of identifying reactive carbonyls generated during vaping and the corresponding DNA adducts formed in the oral cavity.  Human saliva and oral cell samples from e-cigarette users (n=10) and non-user controls (n=10) were obtained to screen reactive carbonyls and DNA adducts. Reactive carbonyls in saliva were derivatized with 2,4-dinitrophenylhydrazine to form hydrazones and analyzed by the NL screening method. Likewise, DNA from oral cells were isolated, hydrolyzed to nucleosides, and analyzed by both targeted and non-targeted DNA adductomics approaches. Using the NL loss screening strategy, increased levels of acrolein, methylglyoxal, and formaldehyde were observed after vaping, while the levels of acetaldehyde and glyoxal vary within subjects possibly due to variations in composition of the e-liquid used. This information was then used to develop targeted and non-targeted DNA adductomics approaches to monitor the corresponding DNA adducts in oral cells of e-cigarette users. Our results showed increased levels of acrolein-derived DNA adducts, in particular, gamma-OH-Acro-dG in e-cigarette users compared to non-users. We are currently investigating other DNA adducts that might be relevant to e-cigarette exposure using non-targeted DNA adductomics approaches and expanding our analysis to a larger sample size.<br/> <br/>

Integrating multi-“omics”- mass spectrometry-based methods to characterize electronic cigarette exposure in humans

256th National Meeting (2018)

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