Increased acrolein-DNA adducts in buccal brushings of e-cigarette users

Increased acrolein-DNA adducts in buccal brushings of e-cigarette users
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DOI:
10.1093/carcin/bgac026
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发表时间:
2022-03-03
期刊:
影响因子:
4.7
通讯作者:
Hecht, Stephen S.
Hecht, Stephen S.
中科院分区:
医学2区
文献类型:
--
作者:
Cheng, Guang;Guo, Jiehong;Hecht, Stephen S.

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每月抽样3个月的20名电子烟使用者的口腔细胞中丙烯醛的DNA加合物显著高于20名非电子烟使用者。这是首次在电子烟使用者的任何组织中发现致癌物-DNA加合物。DNA加合物是遗传毒性物质致癌机制的核心。我们比较了电子烟使用者和非烟草或尼古丁产品使用者口腔细胞DNA中丙烯醛的DNA加合物水平。丙烯醛是一种在电子烟蒸气中发现的遗传毒性致癌物质。电子烟使用者和非使用者每月来我科就诊一次,连续6个月,并采集口腔刷牙和尿液样本。在这项研究中,我们分析了电子烟使用者和非使用者每月三次访问的口腔细胞DNA加合物,通过尿氰乙硫尿酸和总尼古丁当量确认。从口腔刷牙中提取脱氧核糖核酸,用高效液相色谱-纳米电喷雾电离-高分辨串联质谱法分析丙烯醛脱氧核糖核酸加合物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)。电子烟吸烟者DNA加合物的中位数为179fmol/mU·dGuo(范围为5·0~793fmol/mU·dGuo),而非吸烟者的中位数为21.0fmoL/mU·dGuo(范围为5·0~539fmoL/mU·dGuo),P=0.001。这些结果首次表明,电子烟使用者口腔细胞中的致癌物-DNA加合物水平升高。
DNA adducts of acrolein were significantly greater in oral cells of 20 e-cigarette users sampled monthly for 3 months than in 20 non-users. This is the first identification of a carcinogen-DNA adduct in any tissue of an e-cigarette user.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 (gamma-OH-Acr-dGuo). The median value of this DNA adduct in the e-cigarette users was 179 fmol/mu mol dGuo (range 5.0 - 793 fmol/mu mol dGuo) while that for non-users was 21.0 fmol/mu mol dGuo (range 5.0 - 539 fmol/mu mol 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.