4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone is correlated with 8-hydroxy-2′-deoxyguanosine in humans after exposure to environmental tobacco smoke
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone is correlated with 8-hydroxy-2′-deoxyguanosine in humans after exposure to environmental tobacco smoke
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DOI：
10.1016/j.scitotenv.2011.11.039
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发表时间：
2012-01-01
影响因子：
9.8
通讯作者：
Lee, Hui-Ling
中科院分区：
文献类型：
--
作者：
Chiang, Hung-Che;Huang, Yung-Kai;Lee, Hui-Ling
吸烟和暴露于环境烟草烟雾（D'S）是许多癌症的重要危险因素。然而，在人体研究中通常没有对接触剂量进行定量评估。在人体中，4-（甲基亚硝胺）-1-（3-吡啶基）-1-丁醇及其葡萄糖醛酸结合物（定义为总NNAL）是4-（甲基亚硝胺）-1-（3-吡啶基）-1-丁酮（一种嗜热链球菌特异性致癌物）的主要代谢产物。虽然动物研究表明，暴露于香烟烟雾会增加组织氧化DNA损伤，但香烟烟雾和8-羟基脱氧鸟苷（8-OHdG）之间的关系在人类研究中并不一致。在本研究中，我们开发了一种简单、灵敏和耐用的LC-MS/MS方法，用于定量人血浆中总NNAL和8-OHdG浓度。我们定量了121名健康男性受试者血浆中的总NNAL和8-OHdG以及尿液中的8-OHdG。总NNAL水平显着高于吸烟者比从不吸烟者。此外，血浆中的总NNAL水平随着曾经吸烟者每天吸烟的数量而增加。提示血浆中总NNAL是香烟烟雾暴露的良好生物标志物。在按吸烟状况分层并调整年龄、ETS暴露和职业类别后，从不吸烟者的总NNAL与血浆和尿8-OHdG相关，但在曾经吸烟者中不相关。由于非吸烟者的总NNAL水平代表ETS暴露，因此8-OHdG水平似乎与其ETS暴露剂量呈剂量依赖性相关。此外，这种相关性支持的假设，氧化DNA损伤是一个主要的不利影响诱导的ETS暴露在人类。皇冠版权所有（C）2011由Elsevier B. V.出版。保留所有权利。
Cigarette smoking and exposure to environmental tobacco smoke (D'S) are important risk factors for many cancers. However, exposure doses have usually not been quantitatively assessed in human studies. In humans 4(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronate conjugate (defined as total NNAL) are the major metabolites of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, a cigarette-specific carcinogen. Although animal studies have shown that exposure to cigarette smoke increases tissue oxidative DNA damage, the relationship between cigarette smoke and 8-hydroxydeoxyguanosine (8-OHdG) is not consistent in human studies. In the present study, we have developed a simple, sensitive, and robust LC-MS/MS method for quantifying total NNAL and 8-OHdG concentrations in human plasma. We quantified total NNAL and 8-OHdG in plasma as well as 8-OHdG in urine of 121 healthy male subjects. Total NNAL levels were significantly higher in ever-smokers than in never-smokers. Furthermore, total NNAL levels in plasma were increased with numbers of cigarettes smoked per day in ever-smokers. It suggests that total NNAL in plasma is a good biomarker for cigarette smoke exposure. After stratifying by smoking status and adjusting for age, ETS exposure and occupation category, total NNAL was associated with plasma and urinary 8-OHdG in never-smokers, but not in ever-smokers. Since total NNAL levels in nonsmokers represented the ETS exposure, it appears that 8-OHdG levels are dose-dependently correlated with their ETS exposure dose. Furthermore, this correlation supports the hypothesis that oxidative DNA damage is one of major adverse effects induced by ETS exposure in humans. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.