Application of High-Resolution Mass Spectrometry and a Theoretical Model to the Quantification of Multifunctional Carbonyls and Organic Acids in e-Cigarette Aerosol.

Electronic (e-) cigarette aerosol (particle and gas) is a complex mixture of chemicals, of which the profile is highly dependent on device operating parameters and e-liquid flavor formulation. The thermal degradation of the e-liquid solvents propylene glycol and glycerol often generates multifunctional carbonyls that are challenging to quantify because of unavailability of standards. We developed a theoretical method to calculate the relative electrospray ionization sensitivities of hydrazones of organic acids and carbonyls with 2,4-dinitrophenylhydrazine based on their gas-phase basicities (ΔGdeprotonation). This method enabled quantification by high-performance liquid chromatography-high-resolution mass spectrometry HPLC-HRMS in the absence of chemical standards. Accurate mass and tandem multistage MS (MSn) were used for structure identification of vaping products. We quantified five simple carbonyls, six hydroxycarbonyls, four dicarbonyls, three acids, and one phenolic carbonyl in the e-cigarette aerosol with Classic Tobacco flavor. Our results suggest that hydroxycarbonyls, such as hydroxyacetone, lactaldehyde, and dihydroxyacetone can be significant components in e-cigarette aerosols but have received less attention in the literature and have poorly understood health effects. The data support the radical-mediated e-liquid thermal degradation scheme that has been previously proposed and emphasize the need for more research on the chemistry and toxicology of the complex product formation in e-cigarette aerosols.

Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice.

Cancer cells from a primary tumor can disseminate to other tissues, remaining dormant and clinically undetectable for many years. Little is known about the cues that cause these dormant cells to awaken, resume proliferating, and develop into metastases. Studying mouse models, we found that sustained lung inflammation caused by tobacco smoke exposure or nasal instillation of lipopolysaccharide converted disseminated, dormant cancer cells to aggressively growing metastases. Sustained inflammation induced the formation of neutrophil extracellular traps (NETs), and these were required for awakening dormant cancer. Mechanistic analysis revealed that two NET-associated proteases, neutrophil elastase and matrix metalloproteinase 9, sequentially cleaved laminin. The proteolytically remodeled laminin induced proliferation of dormant cancer cells by activating integrin α3ß1 signaling. Antibodies against NET-remodeled laminin prevented awakening of dormant cells. Therapies aimed at preventing dormant cell awakening could potentially prolong the survival of cancer patients.