电子烟是年轻人最常使用的含尼古丁产品。体外研究支持电子烟可能在体内引起细胞压力的潜力；然而，还没有研究证明暴露在电子液雾气溶胶中是否能诱导细胞转化，这是一种与癌前病变强烈相关的过程。我们研究了每周将人支气管上皮细胞系暴露于电子烟雾气中是否会诱导变化并伴随着基因表达和启动子高甲基化的变化。雾化送药系统每周暴露三条支气管上皮细胞系于未经调味的1.2%尼古丁电子液，含尼古丁的3种调味产品或肯塔基参考香烟。使用软琼脂中的集落形成、RNA测序和EPICBeadchip来评价变化、基因组范围内的表达和甲基化变化。詹姆斯敦电子液雾气诱导了HBEC2和HBEC26的变化，而未经调味和蓝色酸甜果汁也诱导了HBEC26的变化。相对于电子烟液体，香烟烟雾气体的变形效率高达电子烟液体的3倍，可以转化HBEC4和HBEC26。变异的克隆体表现出广泛的转录组重编程，香烟和电子烟之间观察到了共同和不同的基因表达变化。电子烟液体诱导的转化对肺癌涉及的经典途径进行了改变，包括轴突指导和NRF2。基因甲基化，在香烟诱导的变异克隆中明显，也影响了詹姆斯敦诱导的HBEC2中的数百个基因。许多表达或表观基因组介导的沉默的基因在吸烟者的肺癌中也受到了影响。这些研究表明，暴露在电子烟雾气中可能会在肺上皮细胞中诱导癌前表型。尽管美国食品和药物管理局禁止销售口味盒装电子烟，但消费者通过其他设备转向了使用口味产品。我们的发现明确支持扩大对主要电子液味道类别的变形潜力的研究，以更好地评估这些复杂混合物的风险。 版权所有 © 2023 Elsevier B.V. 发布。

E-cigarettes are the most commonly used nicotine containing products among youth. In vitro studies support the potential for e-cigarettes to cause cellular stress in vivo; however, there have been no studies to address whether exposure to e-liquid aerosols can induce cell transformation, a process strongly associated with pre-malignancy. We examined whether weekly exposure of human bronchial epithelial cell (HBEC) lines to e-cigarette aerosols would induce transformation and concomitant changes in gene expression and promoter hypermethylation.An aerosol delivery system exposed three HBEC lines to unflavored e-liquid with 1.2% nicotine, 3 flavored products with nicotine, or the Kentucky reference cigarette once a week for 12 weeks. Colony formation in soft agar, RNA-sequencing, and the EPIC Beadchip were used to evaluate transformation, genome-wide expression and methylation changes.Jamestown e-liquid aerosol induced transformation of HBEC2 and HBEC26, while unflavored and Blue Pucker transformed HBEC26. Cigarette smoke aerosol transformed HBEC4 and HBEC26 at efficiencies up to 3-fold greater than e-liquids. Transformed clones exhibited extensive reprogramming of the transcriptome with common and distinct gene expression changes observed between the cigarette and e-liquids. Transformation by e-liquids induced alterations in canonical pathways implicated in lung cancer that included axonal guidance and NRF2. Gene methylation, while prominent in cigarette-induced transformed clones, also affected hundreds of genes in HBEC2 transformed by Jamestown. Many genes with altered expression or epigenetic-mediated silencing were also affected in lung tumors from smokers.These studies show that exposure to e-liquid aerosols can induce a pre-malignant phenotype in lung epithelial cells. While the Food and Drug Administration banned the sale of flavored cartridge-based electric cigarettes, consumers switched to using flavored products through other devices. Our findings clearly support expanding studies to evaluate transformation potency for the major categories of e-liquid flavors to better inform risk from these complex mixtures.Copyright © 2023. Published by Elsevier B.V.