Department of Biochemistry and Molecular Biology, Pennsylvania State University, Hershey, PA 17033, USA.
Cancer Institute, Pennsylvania State University, Hershey, PA 17033, USA.
Int J Environ Res Public Health. 2019 Jul 11;16(14):2468. doi: 10.3390/ijerph16142468.
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.
电子烟气溶胶中的大多数已知致癌物质含量低于烟草烟雾，但许多电子烟使用者也是吸烟者，这些人可能容易受到电子烟可能的促进和/或协同致癌作用的影响。我们研究了电子烟气溶胶（EAC）冷凝物是否有可能增强烟草致癌物质苯并（a）芘（BaP）在人口腔角质细胞系中向遗传毒性产物的代谢。先用两种流行的电子烟的 EAC 预处理细胞，然后用 BaP 处理。通过测量其自发水解产物 BaP 四醇的异构体来测定其最终致癌代谢物反-7,8-二羟基-9,10-环氧-7,8,9,10-四氢 B[a]P（BPDE）的代谢。细胞用 EAC 预处理可使 BaP 四醇的形成速率提高数倍。用电子烟液预处理则增强效果较小。EAC 处理细胞诱导 CYP1A1/1B1 mRNA 和蛋白。用芳基烃受体（AhR）抑制剂α-萘黄酮抑制 BaP 四醇形成的增强，表明 EAC 可能通过激活 AhR 诱导 CYP1A1/1B1 并增强 BaP 代谢。据我们所知，这是首次报道证明电子烟可以增强烟草烟雾致癌物质的遗传毒性作用。
