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.

Yuan-Wan Sun,Joseph B Guttenplan,Wieslawa Kosinska

doi:10.3390/ijerph16142468

Abstract

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 B[a]P (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.

Highlights

E-cigarette (e-cig) usage has become widely prevalent in the U.S and other countries
The effects of blu, and NJOY aerosol condensates, and blu e-liquid on the metabolism of BaP are discussed
BaP is metabolized to a number of products, including isomers of the highly reactive BPDE, which can bind to guanines in DNA and lead to mutations [9,10,11]

Summary

Introduction

E-cigarette (e-cig) usage has become widely prevalent in the U.S and other countries. Studies on e-cig liquids, aerosols and condensates have indicated that they contain much lower levels of known carcinogens than tobacco or tobacco smoke [3], there is little reported research on the effects of e-cig usage on cancer risk in current tobacco users (dual users). A large 2016 study reported a prevalence of 4.5% of e-cig users above 18 years of age in the U.S, corresponding to approximately. A high percentage of younger users are dual users [4,5] In such users, oral cavity tissue will be exposed to the genotoxic effects of tobacco smoke and may be susceptible to promoting or cocarcinogenic effects of other agents, such as e-cigs.

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Discussion

Conclusion