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Metabolism of Carcinogenic Tobacco-Specific Nitrosamines

Principal Investigator: Stephen Hecht

Funding Mechanism: National Institutes of Health- Grant

ID number: 3 R37 CA081301-14S1

Award Date: 9/20/2012

Institution: University of Minnesota Twin Cities


Smokeless tobacco products are accepted causes of oral cavity cancer. Tobacco-specific nitrosamines such as N′-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are recognized as likely causative agents for oral cancer in smokeless tobacco users.  In a recent study, one form of NNN called (S)-NNN was found to be a potent oral cavity carcinogen in rats.  Based on this observation, the goal of this study is to determine the likely role of (S)-NNN as a cause of oral cavity cancer in smokeless tobacco users.  Specific aims are: (1) to quantify levels of (S)-NNN in traditional and emerging smokeless tobacco products; (2) to quantify levels of (S)-NNN and (S)-NNN-N-glucuronide in the urine of smokeless tobacco users; and (3) to develop a new urinary biomarker for assessing NNN uptake in humans. To meet these aims, investigators will analyze 129 product samples representing 29 brands/flavors collected as part of an ongoing research effort and will analyze urine samples collected from 900 smokeless tobacco users. The results of this study will help define the risks associated with smokeless tobacco use and may inform FDA regulation of NNN in smokeless tobacco products.


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