Quantitative Liquid Chromatography-Nanoelectrospray Ionization-High-Resolution Tandem Mass Spectrometry Analysis of Acrolein-DNA Adducts and Etheno-DNA Adducts in Oral Cells from Cigarette Smokers and Nonsmokers.,Chemical Research in Toxicology

当前位置： X-MOL 学术 › Chem. Res. Toxicol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Quantitative Liquid Chromatography-Nanoelectrospray Ionization-High-Resolution Tandem Mass Spectrometry Analysis of Acrolein-DNA Adducts and Etheno-DNA Adducts in Oral Cells from Cigarette Smokers and Nonsmokers.
Chemical Research in Toxicology ( IF 3.7 ) Pub Date : 2020-07-08 , DOI: 10.1021/acs.chemrestox.0c00223
Viviana Paiano ₁ , Laura Maertens ₁ , Valeria Guidolin _{1,

2} , Jing Yang ₃ , Silvia Balbo _{1,

2} , Stephen S Hecht ₁

Affiliation

Cigarette smoking is an important source of human exposure to toxicants and carcinogens and contributes significantly to cancer morbidity and mortality worldwide. Acrolein, a widespread environmental pollutant, is present in relatively high amounts in cigarette smoke and can react directly with DNA to form DNA adducts, which serve as important biomarkers for the assessment of exposure to acrolein and its potential role in smoking related cancer. Etheno-DNA adducts are promutagenic DNA lesions that can derive from exogenous chemicals as well as endogenous sources, including lipid peroxidation. In this study, we developed a combined method for the quantitation of (6R/S)-3-(2′-deoxyribos-1′-yl)-5,6,7,8,-tetrahydro-6-hydroxypyrimido[1,2-a]purine-10(3H)-one (α-OH-Acr-dGuo), (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), 1,N⁶-etheno-dAdo (εdAdo), and 3,N⁴-etheno-dCyd (εdCyd) adducts in oral rinse and cytobrush DNA from smokers and nonsmokers by liquid chromatography–nanoelelctrospray ionization–high-resolution tandem mass spectrometry (LC-NSI-HRMS/MS). For oral rinse samples, there was a statistically significant difference between the levels of α-OH-Acr-dGuo, γ-OH-Acr-dGuo, εdAdo, and εdCyd in smokers (12.1 ± 17.9, 163 ± 227, 182 ± 568, and 194 ± 400 adducts/10⁹ nucleotides, respectively) and nonsmokers (1.85 ± 2.08, 5.95 ± 4.23, 7.69 ± 11.7, and 6.07 ± 10.9 adducts/10⁹ nucleotides, respectively). For cytobrush samples, there was a statistically significant difference between the levels of γ-OH-Acr-dGuo and εdAdo in smokers (259 ± 540 and 82.9 ± 271 adducts/10⁹ nucleotides, respectively) and nonsmokers (7.37 ± 5.09 and 16.2 ± 30.2 adducts/10⁹ nucleotides, respectively) but not for α-OH-Acr-dGuo and εdCyd. Our results demonstrate that oral mucosa cells are an excellent source of material for evaluating DNA adducts to be used as biomarkers of tobacco smoke exposure and molecular changes potentially related to cancer.

中文翻译：

吸烟者和不吸烟者口腔细胞中丙烯醛-DNA 加合物和乙烯-DNA 加合物的定量液相色谱-纳电喷雾电离-高分辨率串联质谱分析。

吸烟是人类接触有毒物质和致癌物的重要来源，并且对全世界癌症发病率和死亡率有重大影响。丙烯醛是一种广泛存在的环境污染物，在香烟烟雾中含量相对较高，可直接与 DNA 反应形成 DNA 加合物，该加合物可作为评估丙烯醛暴露及其在吸烟相关癌症中的潜在作用的重要生物标志物。乙烯-DNA 加合物是一种促突变 DNA 损伤，可能源自外源化学物质以及内源来源，包括脂质过氧化。在本研究中，我们开发了一种定量 (6 R / S )-3-(2′-deoxyribos-1′-yl)-5,6,7,8,-tetrahydro-6-Hydroxypyrimido[1] 的组合方法。 ,2- a ]嘌呤-10( 3H )-酮(α-OH-Acr-dGuo),( 8R / S )-3-(2′-脱氧核糖-1′-基)-5,6,7 ,8,-四氢-8-羟基嘧啶基[1,2- a ]嘌呤-10( 3H )-酮(γ-OH-Acr-dGuo),1, N ^6-乙烯-dAdo(εdAdo),和3,通过液相色谱-纳米电喷雾电离-高分辨率串联质谱 (LC-NSI-HRMS/MS) 检测吸烟者和非吸烟者口腔冲洗液和细胞刷 DNA 中的N ⁴ -乙烯-dCyd (εdCyd) 加合物。对于口腔冲洗液样品，吸烟者的 α-OH-Acr-dGuo、γ-OH-Acr-dGuo、εdAdo 和 εdCyd 水平存在统计学显着差异（12.1 ± 17.9、163 ± 227、182 ± 568、和194±400个加合物/10 ^{9 个}核苷酸）和非吸烟者（分别为1.85±2.08、5.95±4.23、7.69±11.7和6.07±10.9个加合物/10 ^{9 个}核苷酸）。对于细胞刷样本，吸烟者（分别为 259 ± 540 和 82.9 ± 271 加合物/10 ^{9 个}核苷酸）和非吸烟者（7.37 ± 5.09 和 16.2 ±分别为 30.2 个加合物/10 ^{9 个}核苷酸），但不适用于 α-OH-Acr-dGuo 和 εdCyd。我们的结果表明，口腔粘膜细胞是评估 DNA 加合物的极好材料来源，该加合物可用作烟草烟雾暴露和可能与癌症相关的分子变化的生物标志物。

更新日期：2020-08-17

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11