Abstract

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that is involved in multiple cellular pathways, including inflammatory signaling, estrogen signaling, and tumorigenesis. Some AHR-regulated genes are associated with the bioactivation of certain carcinogens, such as the environmental contaminant, benzo[a]pyrene (B[a]P). Cigarette smoke condensate (CSC), which contains high levels of B[a]P, has therefore also been shown to activate the AHR. Since e-cigarettes have become a popular alternative to conventional smoking, e-cigarette vapor oils were investigated here to see how they compared to CSC in terms of AHR activation in human liver cells. Dietary bioflavonoids, such as quercetin, also bind to the AHR but exhibit a much lower AHR activation than B[a]P, suggesting that it may be useful as a competitive inhibitor. Utilizing a luciferase reporter assay, we observed a significantly lower level of AHR activation from e-cigarette oils (either with or without nicotine) compared to CSC. Our results also indicate that cells co-treated with 100µM quercetin and CSC were significantly lower in activation of the AHR than CSC alone. These findings suggests that e-cigarette vapor oils do not expose individuals to high levels of AHR-associated carcinogens, like conventional cigarettes, and may pose a lower risk for the development of lung cancer in smokers. Similarly, including quercetin in the diet may protect against certain aspects of carcinogenesis in humans.