Presence of the Carcinogen N′-Nitrosonornicotine in Saliva of E-cigarette Users

Gabriela Bustamante, Bin Ma, Galina Yakovlev, Katrina Yershova, Chap T Le, Joni Jensen, Dorothy K Hatsukami, Irina Stepanov

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Many harmful constituents are present in e-cigarettes at much lower levels than in cigarette smoke, and the results of analysis of urinary biomarkers in e-cigarette users are consistent with these findings. However, understanding the health effects of chronic exposures to e-cigarette aerosols may require thinking beyond these comparisons. In this study, we investigated the endogenous formation of the tobacco-specific oral and esophageal carcinogen N′-nitrosonornicotine (NNN) in e-cigarette users. Salivary NNN, nornicotine, and nicotine as well as urinary tobacco biomarkers, including total NNN, were analyzed in 20 e-cigarette users, 20 smokers, and 19 nonsmokers. Nornicotine and NNN levels in e-cigarettes used by the study participants were also analyzed. The mean of NNN in saliva of e-cigarette users was 14.6 (±23.1) pg/mL, ranging from nonquantifiable (below the limit of quantitation, LOQ) to 76.0 pg/mL. In smokers, salivary NNN ranged from below LOQ to 739 pg/mL, with 80% of smokers having salivary NNN in the range of levels found in e-cigarette users. Consistent with a previous report, very low levels of urinary total NNN were present in only 5 out of 20 e-cigarette users (ranging from 0.001 to 0.01 pmol/mL urine). Only trace levels of NNN were found in e-cigarette liquids. Together, our findings demonstrate that NNN is formed endogenously in e-cigarette users. While the overall exposure to NNN in e-cigarette users is dramatically lower than in smokers, the known carcinogenic potency of NNN warrants further investigations into the potential consequences of its endogenous formation. Salivary NNN, rather than urinary total NNN, which accounts for only 1-3% of the NNN dose, should be used to monitor e-cigarette users' exposure to this carcinogen.

Original languageEnglish (US)
Pages (from-to)731-738
Number of pages8
JournalChemical research in toxicology
Volume31
Issue number8
DOIs
StatePublished - Aug 20 2018

Bibliographical note

Funding Information:
This study was supported by the National Cancer Institute of the National Institutes of Health and the Center for Tobacco Products of the Food and Drug Administration under Award Number R01CA180880. LC-MS/MS was carried out in the Analytical Biochemistry Shared Resource of the Masonic Cancer Center, supported in part by Grant CA-77598 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Food and Drug Administration.

Funding Information:
*Address: Masonic Cancer Center, University of Minnesota, CCRB 2-140, 2231 Sixth Street SE, Minneapolis, MN 55455. Phone: (612) 624-4998. Fax: (612) 626-5135. E-mail: stepa011@umn.edu. ORCID Bin Ma: 0000-0002-7549-2658 Irina Stepanov: 0000-0001-5140-8944 Funding This study was supported by the National Cancer Institute of the National Institutes of Health and the Center for Tobacco Products of the Food and Drug Administration under Award Number R01CA180880. LC−MS/MS was carried out in the Analytical Biochemistry Shared Resource of the Masonic Cancer Center, supported in part by Grant CA-77598 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Food and Drug Administration. Notes The authors declare no competing financial interest.

Publisher Copyright:
© 2018 American Chemical Society.

Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.

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