Metabolism of N'-nitrosonornicotine enantiomers by cultured rat esophagus and in vivo in rats.

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摘要：

People who use tobacco products are exposed to considerable amounts of N'-nitrosonornicotine (NNN), a well-established esophageal carcinogen in rats. NNN is believed to play a significant role as a cause of esophageal and oral cavity cancer in smokers and snuff dippers. The carcinogenicity of NNN is dependent on its metabolic activation. However, virtually all studies carried out to date on NNN metabolism have used racemic material. In this study, we examined the metabolism of [5-3H]-(S)-NNN and [5-3H]-(R)-NNN in cultured rat esophagus and in vivo in rats. Cultured rat esophagus metabolized (S)-NNN (1 μM) predominantly to products of 2'-hydroxylation, 4-oxo-4-(3-pyridyl)butanoic acid (keto acid) and 4-hydroxy-1-(3-pyridyl)-1-butanone (keto alcohol). In contrast, the major metabolite of (R)-NNN under these conditions was 4-hydroxy-4-(3-pyridyl)butanoic acid (hydroxy acid), a product of NNN 5'-hydroxylation. The 2'-hydroxylation:5'-hydroxylation metabolite ratio ranged from 6.22 to 8.06 at various time inte...

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关键词：

Nitrosamines Tobacco Smokeless N' nitrosonornicotine 亚硝胺类烟草非吸烟

DOI：

10.1021/tx990171l

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年份：

2010