Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli County, Taiwan, ROC.
Sci Total Environ. 2012 Jan 1;414:134-9. doi: 10.1016/j.scitotenv.2011.11.039. Epub 2011 Dec 3.
Cigarette smoking and exposure to environmental tobacco smoke (ETS) 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.
吸烟和环境烟草烟雾（ETS）暴露是许多癌症的重要危险因素。然而，在人类研究中，通常没有对暴露剂量进行定量评估。在人类中，4-（甲基亚硝氨基）-1-（3-吡啶基）-1-丁醇及其葡萄糖醛酸缀合物（定义为总 NNAL）是香烟特异性致癌物 4-（甲基亚硝氨基）-1-（3-吡啶基）-1-丁酮的主要代谢物。尽管动物研究表明，暴露于香烟烟雾会增加组织氧化 DNA 损伤，但在人类研究中，香烟烟雾与 8-羟基脱氧鸟苷（8-OHdG）之间的关系并不一致。在本研究中，我们开发了一种简单、灵敏、稳健的 LC-MS/MS 方法，用于定量测定人血浆中的总 NNAL 和 8-OHdG 浓度。我们定量测定了 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。在曾经吸烟者中，总 NNAL 水平明显高于从不吸烟者。此外，在曾经吸烟者中，每日吸烟量与血浆中总 NNAL 水平呈正相关。这表明，血浆中的总 NNAL 是香烟烟雾暴露的良好生物标志物。根据吸烟状况进行分层，并调整年龄、ETS 暴露和职业类别后，在从不吸烟者中，总 NNAL 与血浆和尿液中的 8-OHdG 相关，但在曾经吸烟者中不相关。由于非吸烟者的总 NNAL 水平代表了 ETS 暴露，因此 8-OHdG 水平似乎与他们的 ETS 暴露剂量呈剂量依赖性相关。此外，这种相关性支持了这样一种假设，即氧化 DNA 损伤是 ETS 暴露在人类中引起的主要不良影响之一。
