Skip to main content

Main menu

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
    • Front Matter Portal
    • Journal Club
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home
  • Log in
  • My Cart

Advanced Search

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
    • Front Matter Portal
    • Journal Club
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
Letter

Assessment of E-cigarette impact on smokers: The importance of experimental conditions relevant to human consumption

View ORCID ProfileGiovanni Li Volti, Riccardo Polosa, and Massimo Caruso
  1. aDepartment of Biomedical and Biotechnological Sciences, University of Catania, 95125 Catania, Italy;
  2. bDepartment of Clinical and Experimental Medicine, University of Catania, 95125 Catania, Italy

See allHide authors and affiliations

PNAS April 3, 2018 115 (14) E3073-E3074; first published March 13, 2018; https://doi.org/10.1073/pnas.1801967115
Giovanni Li Volti
aDepartment of Biomedical and Biotechnological Sciences, University of Catania, 95125 Catania, Italy;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Giovanni Li Volti
  • For correspondence: livolti@unict.it
Riccardo Polosa
bDepartment of Clinical and Experimental Medicine, University of Catania, 95125 Catania, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Massimo Caruso
bDepartment of Clinical and Experimental Medicine, University of Catania, 95125 Catania, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • PDF
Loading

We read with great interest the work of Lee et al. (1), in which the authors measured DNA damage induced by nitrosamines in vitro in different cell types and in vivo in various organs of E-cigarette smoke-exposed mice. The authors conclude that E-cigarette smoke might contribute to lung and bladder cancer in humans.

We do agree with the data interpretation of Lee et al. (1) based on their experimental evidence, but we do not share their conclusions about the possibility of translating these results into real-life settings. The present study does not replicate normal conditions of use and lacks standardized protocols for E-cigarette aerosol exposure and dosimetry. To this regard, animal studies and in vitro systems often include chronic, high-dose exposures and do not approximate the type of exposure from human vaping, thus leading to extreme overestimation of toxicological effects (2).

In fact, if we consider that the overall bodyweight of the mice is about 25 g, then the daily dose of aerosol exposure in mice would appear to be at least 3,000 times higher than that of an average vaper of 75 kg (i.e., 75,000 g). This would imply nothing but intoxication from the aerosol mass and its content. In this regard, Waldum et al. (3) showed no microscopic or macroscopic lung tumors, nor any increase in pulmonary neuroendocrine cells, following long-term inhalation of nicotine. To explain such evident discrepancy between the two studies, it is important to note that rodents were exposed to much different levels of nicotine. This is a very important issue when using an animal model in the attempt to resemble the conditions of a real-life setting. In particular, the study of Waldum et al. (3) exposed animals to nicotine (100 ng/mL), giving twice the plasma concentration found in heavy smokers. In contrast, in the present study Lee et al. (1) exposed mice to nicotine (10 mg/mL) without reporting its plasma concentration in animals.

In addition, in vitro experimental conditions may not resemble those of humans. In particular, cell irradiation with UV (i.e., 1,500 J/m2) seems to be much higher compared with other reports (i.e., 0.6 J/m2) (4). As far as concerns pharmacological treatment, Lee et al. (1) used very different nicotine concentrations (BEAS-2B: 0, 100, 300, 1,000 μM; UROtsa: 0, 50, 100, 200 μM), which appear to be very high compared with other experimental conditions (i.e., 0.5 μM) (5). Similarly, nicotine-derived nitrosamine ketone concentrations 0, 10, 300, and 1,000 μM were very high compared with other previous reports (0.1 μM) (6). Finally, the positive evidence from real-life surveys and clinical studies of patients with respiratory conditions supporting health benefits with E-cigarette use is in stark contrast with the concerns raised in animal models (7). By placing a greater emphasis on potential risks of E-cigarette use, Lee et al. (1) fail to acknowledge that they may represent a major opportunity for individual as well as public health.

Footnotes

  • ↵1To whom correspondence should be addressed. Email: livolti{at}unict.it.
  • Author contributions: R.P. analyzed data; and G.L.V. and M.C. wrote the paper.

  • Conflict of interest statement: R.P. is a full-time employee of the University of Catania, Italy. In relation to his work in the area of tobacco control, R.P. has received lecture fees and research funding from Pfizer and GlaxoSmithKline, manufacturers of stop-smoking medications. He has also served as a consultant for Pfizer, Global Health Alliance for treatment of tobacco dependence, Electronic Cigarette Industry Trade Association, UK, and Health Diplomats. Lecture fees from a number of European electronic cigarette industry and trade associations (including FIVAPE in France and FIESEL in Italy) were directly donated to Vaper Advocacy no-profit organizations. Although no research was ever funded by the industry, support contributing to publication/open access costs of the following papers was received by the e-cig/e-liquid industry: Happy Liquid for https://www.ncbi.nlm.nih.gov/pubmed/28337155; Ritchy Europe for https://www.ncbi.nlm.nih.gov/pubmed/27845734; Cuts Ice e-Liquid Laboratories for https://www.ncbi.nlm.nih.gov/pubmed/28477286; and VDLV e-Liquids for https://www.ncbi.nlm.nih.gov/pubmed/28362360. R.P. is currently Scientific Advisor for LIAF, Lega Italiana Anti Fumo (Italian acronym for Italian Anti-Smoking League) and Head of the European Technical Committee for standardization on'Requirements and test methods for emissions of electronic cigarettes' (CEN/TC 437; WG4).

Published under the PNAS license.

References

  1. ↵
    1. Lee H-W, et al.
    (2018) E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart, and bladder as well as in human lung and bladder cells. Proc Natl Acad Sci USA 115:E1560–E1569.
    OpenUrlAbstract/FREE Full Text
  2. ↵
    1. Caruso M,
    2. Mendelsohn CP,
    3. Polosa R
    (2017) Letter to the Editor: Pulmonary toxicity of electronic cigarettes: More doubts than certainties. Am J Physiol Lung Cell Mol Physiol 313:L964–L965.
    OpenUrlCrossRefPubMed
  3. ↵
    1. Waldum HL, et al.
    (1996) Long-term effects of inhaled nicotine. Life Sci 58:1339–1346.
    OpenUrlCrossRefPubMed
  4. ↵
    1. Alderton GK, et al.
    (2006) Regulation of mitotic entry by microcephalin and its overlap with ATR signalling. Nat Cell Biol 8:725–733.
    OpenUrlCrossRefPubMed
  5. ↵
    1. Nishioka T, et al.
    (2011) Nicotine overrides DNA damage-induced G1/S restriction in lung cells. PLoS One 6:e18619.
    OpenUrlPubMed
  6. ↵
    1. Wu Q,
    2. Nadesalingam J,
    3. Moodley S,
    4. Bai X,
    5. Liu M
    (2015) XB130 translocation to microfilamentous structures mediates NNK-induced migration of human bronchial epithelial cells. Oncotarget 6:18050–18065.
    OpenUrlCrossRefPubMed
  7. ↵
    1. Morjaria JB,
    2. Mondati E,
    3. Polosa R
    (2017) E-cigarettes in patients with COPD: Current perspectives. Int J Chron Obstruct Pulmon Dis 12:3203–3210.
    OpenUrl
PreviousNext
Back to top
Article Alerts
Email Article

Thank you for your interest in spreading the word on PNAS.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Assessment of E-cigarette impact on smokers: The importance of experimental conditions relevant to human consumption
(Your Name) has sent you a message from PNAS
(Your Name) thought you would like to see the PNAS web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Assessment of E-cigarette impact on smokers: The importance of experimental conditions relevant to human consumption
Giovanni Li Volti, Riccardo Polosa, Massimo Caruso
Proceedings of the National Academy of Sciences Apr 2018, 115 (14) E3073-E3074; DOI: 10.1073/pnas.1801967115

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Assessment of E-cigarette impact on smokers: The importance of experimental conditions relevant to human consumption
Giovanni Li Volti, Riccardo Polosa, Massimo Caruso
Proceedings of the National Academy of Sciences Apr 2018, 115 (14) E3073-E3074; DOI: 10.1073/pnas.1801967115
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley

Article Classifications

  • Biological Sciences
  • Medical Sciences

This Letter has a Reply and related content. Please see:

  • Relationship between Letter and Reply - March 13, 2018
  • E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart, and bladder as well as in human lung and bladder cells - January 29, 2018
Proceedings of the National Academy of Sciences: 115 (14)
Table of Contents

Submit

Sign up for Article Alerts

Jump to section

  • Article
    • Footnotes
    • References
  • Info & Metrics
  • PDF

You May Also be Interested in

Setting sun over a sun-baked dirt landscape
Core Concept: Popular integrated assessment climate policy models have key caveats
Better explicating the strengths and shortcomings of these models will help refine projections and improve transparency in the years ahead.
Image credit: Witsawat.S.
Model of the Amazon forest
News Feature: A sea in the Amazon
Did the Caribbean sweep into the western Amazon millions of years ago, shaping the region’s rich biodiversity?
Image credit: Tacio Cordeiro Bicudo (University of São Paulo, São Paulo, Brazil), Victor Sacek (University of São Paulo, São Paulo, Brazil), and Lucy Reading-Ikkanda (artist).
Syrian archaeological site
Journal Club: In Mesopotamia, early cities may have faltered before climate-driven collapse
Settlements 4,200 years ago may have suffered from overpopulation before drought and lower temperatures ultimately made them unsustainable.
Image credit: Andrea Ricci.
Steamboat Geyser eruption.
Eruption of Steamboat Geyser
Mara Reed and Michael Manga explore why Yellowstone's Steamboat Geyser resumed erupting in 2018.
Listen
Past PodcastsSubscribe
Birds nestling on tree branches
Parent–offspring conflict in songbird fledging
Some songbird parents might improve their own fitness by manipulating their offspring into leaving the nest early, at the cost of fledgling survival, a study finds.
Image credit: Gil Eckrich (photographer).

Similar Articles

Site Logo
Powered by HighWire
  • Submit Manuscript
  • Twitter
  • Facebook
  • RSS Feeds
  • Email Alerts

Articles

  • Current Issue
  • Special Feature Articles – Most Recent
  • List of Issues

PNAS Portals

  • Anthropology
  • Chemistry
  • Classics
  • Front Matter
  • Physics
  • Sustainability Science
  • Teaching Resources

Information

  • Authors
  • Editorial Board
  • Reviewers
  • Subscribers
  • Librarians
  • Press
  • Site Map
  • PNAS Updates
  • FAQs
  • Accessibility Statement
  • Rights & Permissions
  • About
  • Contact

Feedback    Privacy/Legal

Copyright © 2021 National Academy of Sciences. Online ISSN 1091-6490