Evidence for endogenous formation of N'-nitrosonornicotine in some long-term nicotine patch users
Evidence for endogenous formation of N'-nitrosonornicotine in some long-term nicotine patch users
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DOI：
10.1093/ntr/ntn004
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发表时间：
2009-01-01
影响因子：
4.7
通讯作者：
Hecht, Stephen S.
中科院分区：
文献类型：
--
作者：
Stepanov, Irina;Carmella, Steven G.;Hecht, Stephen S.
尼古丁或其代谢物在人体内的亚硝化作用可导致2种致癌的烟草特异性亚硝胺- 025efn′-亚硝基烟碱（NNN）和4-（甲基亚硝胺）-1-（3-吡啶基）-1-丁酮（NNK）的形成。我们调查了戒烟并使用21毫克尼古丁贴片6个月的人内源性NNN形成的可能性。我们量化了尿中暴露于NNN- 025ef的生物标志物，即NNN及其吡啶- n -葡糖苷的总和，即总NNN。同时测定NNK代谢物- 025ef4 -（甲基亚硝胺）-1-（3-吡啶基）-1-丁醇（NNAL）及其N-和o -葡萄糖醛酸盐的总和，称为总NNAL。尿总NNN的平均下降幅度小于总NNAL的下降幅度：戒烟和使用贴片24周后，尿中检测到22%的基线总NNN和7.3%的基线总NNAL （p = 0.02）。使用尼古丁贴片24周后，相同尿液样本中总NNN与总NNAL的平均比率从基线尿液中的0.14增加到0.38。总的来说，这些结果表明尼古丁贴片使用者可能会内源性形成NNN。然而，在使用贴片期间，尿总NNN水平通常极低。此外，在本文分析的20名受试者中，有10名受试者的总NNN下降率与总NNAL下降率相似，表明这些受试者中几乎不存在内源性NNN形成。补充抗坏血酸可能是阻断尼古丁贴片使用者可能形成的神经网络的简单方法。
Nitrosation of nicotine or its metabolites in the human body could lead to formation of the 2 carcinogenic tobacco-specific nitrosamines-025EFN'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).We investigated the possibility of endogenous formation of NNN in people who had stopped smoking and used the 21-mg nicotine patch for 6 months. We quantified urinary biomarkers of exposure to NNN-025EFthe sum of NNN and its pyridine-N-glucuronide, referred to as total NNN. Also measured were NNK metabolites-025EFthe sum of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its N- and O-glucuronides, referred to as total NNAL.The average decline of urinary total NNN was less drastic than that of total NNAL: 22% of baseline total NNN and 7.3% of baseline total NNAL were detected in urine 24 weeks after smoking cessation and patch use (p = .02). The average ratio of total NNN to total NNAL in the same urine samples increased from 0.14 in baseline urine to 0.38 after 24 weeks of nicotine patch use.Overall, these results demonstrate that endogenous formation of NNN may occur in nicotine patch users. However, the levels of urinary total NNN during patch use were generally extremely low. Moreover, in 10 of 20 subjects analyzed here, the rate of decline in total NNN was similar to that in total NNAL, indicating that endogenous formation of NNN is virtually nonexistent in these subjects. Supplementation with ascorbic acid could be a simple approach to block possible NNN formation in nicotine patch users.