Cheng Guang, Guo Jiehong, Carmella Steven G, Lindgren Bruce, Ikuemonisan Joshua, Niesen Brittany, Jensen Joni, Hatsukami Dorothy K, Balbo Silvia, Hecht Stephen S
Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
Carcinogenesis. 2022 Jun 4;43(5):437-444. doi: 10.1093/carcin/bgac026.
DNA adducts are central in the mechanism of carcinogenesis by genotoxic agents. We compared levels of a DNA adduct of acrolein, a genotoxic carcinogen found in e-cigarette vapor, in oral cell DNA of e-cigarette users and non-users of any tobacco or nicotine product. e-Cigarette users and non-users visited our clinic once monthly for 6 months, and oral brushings and urine samples were collected. For this study, we analyzed oral cell DNA adducts from three monthly visits in e-cigarette users and non-users as confirmed by urinary cyanoethyl mercapturic acid and total nicotine equivalents. DNA was isolated from the oral brushings and analyzed by a validated liquid chromatography-nanoelectrospray ionization-high resolution tandem mass spectrometry method for the acrolein DNA adduct 8R/S-3-(2'-deoxyribos-1'-yl)-5,6,7,8-tetrahydro-8-hydroxypyrimido[1,2-a]purine-10-(3H)-one (γ-OH-Acr-dGuo). The median value of this DNA adduct in the e-cigarette users was 179 fmol/µmol dGuo (range 5.0 - 793 fmol/µmol dGuo) while that for non-users was 21.0 fmol/µmol dGuo (range 5.0 - 539 fmol/µmol dGuo), P = 0.001. These results demonstrate for the first time that e-cigarette users have elevated levels of a carcinogen-DNA adduct in their oral cells.
DNA加合物在遗传毒性剂致癌机制中起着核心作用。我们比较了电子香烟使用者与不使用任何烟草或尼古丁产品者口腔细胞DNA中丙烯醛（一种在电子烟烟雾中发现的遗传毒性致癌物）的DNA加合物水平。电子香烟使用者和非使用者连续6个月每月到我们诊所一次，采集口腔擦拭样本和尿液样本。在本研究中，我们分析了电子香烟使用者和非使用者三个月访视时的口腔细胞DNA加合物，尿中氰基乙基巯基尿酸和总尼古丁当量可证实其使用情况。从口腔擦拭样本中分离DNA，并通过经过验证的液相色谱-纳米电喷雾电离-高分辨率串联质谱法分析丙烯醛DNA加合物8R/S-3-(2'-脱氧核糖-1'-基)-5,6,7,8-四氢-8-羟基嘧啶并[1,2-a]嘌呤-10-(3H)-酮（γ-OH-Acr-dGuo）。电子香烟使用者中该DNA加合物的中位数为179 fmol/µmol dGuo（范围5.0 - 793 fmol/µmol dGuo），而非使用者为21.0 fmol/µmol dGuo（范围5.0 - 539 fmol/µmol dGuo），P = 0.001。这些结果首次证明电子香烟使用者口腔细胞中致癌物-DNA加合物水平升高。
