PMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000, Neuchâtel, Switzerland.
PMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000, Neuchâtel, Switzerland.
Food Chem Toxicol. 2019 Jan;123:501-510. doi: 10.1016/j.fct.2018.11.020. Epub 2018 Nov 9.
Cigarette smoke (CS) exposure has been shown to correlate with changes in DNA methylation levels, however, the impact of CS on DNA methylation at genome-wide scale is missing. Here, we used whole-genome bisulfite sequencing to assess the effects of CS extract and aerosol from the Tobacco Heating System (THS) 2.2, a candidate modified risk tobacco product, on DNA methylation in lung and liver tissues from apolipoprotein E-deficient mice during an eight-month period of exposure. We found that in lung tissue, CS mainly induced hypermethylation of candidate enhancers at late time points, while promoters were less affected. This effect was strongly reduced upon cessation or switching to THS 2.2. By contrast, chronic exposure to THS 2.2 had a limited effect on DNA methylation at both promoters and enhancers. We also identified members of the Ets and Fox families of transcription factors as potential players in the epigenetic response to CS exposure in lung tissue. In contrast to the lung, DNA methylation in the liver was largely insensitive to all investigated exposures. In summary, our investigations indicate that CS-related DNA methylation alterations are tissue-specific, occur mainly at enhancers and are strongly reduced upon smoking cessation or switching to THS2.2.
香烟烟雾（CS）暴露已被证明与 DNA 甲基化水平的变化相关，然而，CS 对全基因组范围内 DNA 甲基化的影响尚不清楚。在这里，我们使用全基因组亚硫酸氢盐测序来评估 CS 提取物和来自加热不燃烧系统 2.2（一种候选改良风险烟草产品）的气溶胶对载脂蛋白 E 缺陷小鼠肺和肝组织中 DNA 甲基化的影响，在长达八个月的暴露期间。我们发现，在肺组织中，CS 主要在晚期诱导候选增强子的超甲基化，而启动子受影响较小。这种效应在停止或切换到 THS 2.2 时会大大减弱。相比之下，慢性暴露于 THS 2.2 对启动子和增强子的 DNA 甲基化影响有限。我们还鉴定了 Ets 和 Fox 转录因子家族的成员，作为肺组织中对 CS 暴露的表观遗传反应的潜在参与者。与肺组织相比，肝脏中的 DNA 甲基化对所有研究的暴露均不敏感。总之，我们的研究表明，CS 相关的 DNA 甲基化改变是组织特异性的，主要发生在增强子上，并且在戒烟或切换到 THS2.2 时会大大减少。
