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人血红蛋白中N-烷基化氨基酸的分析:吸烟者中N-甲基缬氨酸水平升高的证据。

Analysis of N-alkylated amino acids in human hemoglobin: evidence for elevated N-methylvaline levels in smokers.

作者信息

Bader M, Lewalter J, Angerer J

机构信息

Institute and Clinic of Occupational, Social and Environmental Medicine, University of Erlangen-Nümberg, Germany.

出版信息

Int Arch Occup Environ Health. 1995;67(4):237-42. doi: 10.1007/BF00409405.

DOI:10.1007/BF00409405
PMID:7591184
Abstract

To investigate the contribution of cigarette smoking to the levels of N-methylvaline and N-hydroxyethylvaline in hemoglobin we analyzed samples from 32 smokers and 37 nonsmokers. The average background levels of the nonsmoking individuals were determined to be 1175 +/- 176 pmol N-methylvaline/g globin, ranging from 722 to 1516 pmol/g globin, and 46 +/- 12 pmol N-hydroxyethylvaline/g globin, ranging from 19 to 64 pmol/g globin. A significant correlation (P < 0.001) was found between both amino acids and the amount of cigarettes smoked per day, with an increase of 42 pmol N-methylvaline/g globin/cigarette per day and 11 pmol N-hydroxyethylvaline/g globin/cigarette per day. No influence of age, sex, and occupational exposure was observed. Furthermore, the levels of N-hydroxyethylvaline and N-methylvaline correlated for smokers but not for nonsmokers, indicating cigarette smoking as a common source for both adducts. To our knowledge, this is the first time N-methylvaline levels are reported to differ significantly between smokers and nonsmokers in the general population. Especially the analysis of N-methylvaline following low-level exposures to methylating agents should therefore take into consideration the influence of individual smoking habits. Additionally, the results of our study confirm the reliability of N-hydroxyethylvaline as an indicator of individual cigarette consumption. We successfully applied a new calibration technique to the analysis of N-hydroxyethylvaline, introducing a commercially available and well-defined dipeptide standard. The observed levels of N-hydroxyethylvaline in the samples are in line with those reported in the literature and verify the applicability of our calibration method.

摘要

为了研究吸烟对血红蛋白中N-甲基缬氨酸和N-羟乙基缬氨酸水平的影响,我们分析了32名吸烟者和37名不吸烟者的样本。非吸烟个体的平均背景水平确定为1175±176 pmol N-甲基缬氨酸/克球蛋白,范围为722至1516 pmol/克球蛋白,以及46±12 pmol N-羟乙基缬氨酸/克球蛋白,范围为19至64 pmol/克球蛋白。发现这两种氨基酸与每日吸烟量之间存在显著相关性(P<0.001),每天每支香烟导致N-甲基缬氨酸/克球蛋白增加42 pmol,N-羟乙基缬氨酸/克球蛋白增加11 pmol。未观察到年龄、性别和职业暴露的影响。此外,吸烟者中N-羟乙基缬氨酸和N-甲基缬氨酸的水平相关,但不吸烟者中不相关,表明吸烟是这两种加合物的共同来源。据我们所知,这是首次报道一般人群中吸烟者和不吸烟者之间N-甲基缬氨酸水平存在显著差异。因此,在低水平接触甲基化剂后分析N-甲基缬氨酸时,应考虑个体吸烟习惯的影响。此外,我们的研究结果证实了N-羟乙基缬氨酸作为个体香烟消费量指标的可靠性。我们成功地将一种新的校准技术应用于N-羟乙基缬氨酸的分析,引入了一种市售的、定义明确的二肽标准品。样本中观察到的N-羟乙基缬氨酸水平与文献报道的水平一致,并验证了我们校准方法的适用性。

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