Department of Environmental Medicine, New York University School of Medicine, Tuxedo Park, NY 10987.
Department of Urology, New York University School of Medicine, New York, NY 10016.
Proc Natl Acad Sci U S A. 2018 Feb 13;115(7):E1560-E1569. doi: 10.1073/pnas.1718185115. Epub 2018 Jan 29.
E-cigarette smoke delivers stimulant nicotine as aerosol without tobacco or the burning process. It contains neither carcinogenic incomplete combustion byproducts nor tobacco nitrosamines, the nicotine nitrosation products. E-cigarettes are promoted as safe and have gained significant popularity. In this study, instead of detecting nitrosamines, we directly measured DNA damage induced by nitrosamines in different organs of E-cigarette smoke-exposed mice. We found mutagenic O-methyldeoxyguanosines and γ-hydroxy-1 -propano-deoxyguanosines in the lung, bladder, and heart. DNA-repair activity and repair proteins XPC and OGG1/2 are significantly reduced in the lung. We found that nicotine and its metabolite, nicotine-derived nitrosamine ketone, can induce the same effects and enhance mutational susceptibility and tumorigenic transformation of cultured human bronchial epithelial and urothelial cells. These results indicate that nicotine nitrosation occurs in vivo in mice and that E-cigarette smoke is carcinogenic to the murine lung and bladder and harmful to the murine heart. It is therefore possible that E-cigarette smoke may contribute to lung and bladder cancer, as well as heart disease, in humans.
电子烟烟雾以气溶胶的形式输送刺激物尼古丁，而无需使用烟草或燃烧过程。它既不含致癌的不完全燃烧副产物，也不含烟草亚硝胺，即尼古丁亚硝化产物。电子烟被宣传为安全产品，并获得了广泛的关注。在这项研究中，我们没有检测亚硝胺，而是直接测量了电子烟烟雾暴露的小鼠不同器官中由亚硝胺引起的 DNA 损伤。我们在肺、膀胱和心脏中发现了致突变的 O-甲基脱氧鸟苷和γ-羟基-1-丙基脱氧鸟苷。肺中的 DNA 修复活性和修复蛋白 XPC 和 OGG1/2 显著降低。我们发现尼古丁及其代谢物尼古丁衍生的亚硝胺酮可以诱导相同的效应，并增强培养的人支气管上皮细胞和尿路上皮细胞的突变易感性和肿瘤转化。这些结果表明，尼古丁亚硝化在小鼠体内发生，电子烟烟雾对小鼠的肺和膀胱具有致癌性，并对小鼠的心脏有害。因此，电子烟烟雾可能会导致人类患肺癌、膀胱癌和心脏病。
