E-cigarette Aerosol Condensate Enhances Metabolism of Benzo(a)pyrene to Genotoxic Products, and Induces CYP1A1 and CYP1B1, Likely by Activation of the Aryl Hydrocarbon Receptor

E-cigarette aerosol contains lower levels of most known carcinogens than tobacco smoke, but many users of e-cigarettes are also smokers, and these individuals may be vulnerable to possible promoting and/or cocarcinogenic effects of e-cigarettes. We investigated the possibility that a condensate of e-cigarette aerosol (EAC) enhances the metabolism of the tobacco carcinogen, benzo(a)pyrene (BaP), to genotoxic products in a human oral keratinocyte cell line. Cells were pretreated with EAC from two popular e-cigs and then with BaP. Metabolism to its ultimate carcinogenic metabolite, anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro BaP (BPDE), was assayed by measuring isomers of its spontaneous hydrolysis products, BaP tetrols. The pretreatment of cells with EAC enhanced the rate of BaP tetrol formation several fold. Pretreatment with the e-liquid resulted in a smaller enhancement. The treatment of cells with EAC induced CYP1A1/1B1 mRNA and protein. The enhancement of BaP tetrol formation was inhibited by the aryl hydrocarbon receptor (AhR) inhibitor, α-napthoflavone, indicating EAC likely induces CYP1A1/1B1 and enhances BaP metabolism by activating the AhR. To our knowledge, this is first report demonstrating that e-cigarettes can potentiate the genotoxic effects of a tobacco smoke carcinogen.