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Nicotine exposure potentiates lung tumorigenesis by perturbing cellular surveillance
BACKGROUND: Nicotine is a major tobacco component and found at circulating concentrations in smokers’ bloodstreams. Although considered a non-carcinogenic substance, nicotine rapidly defuses to tissues after being inhaled, inviting effects on cellular physiology, particularly in the lung. Widespread...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078213/ https://www.ncbi.nlm.nih.gov/pubmed/32001831 http://dx.doi.org/10.1038/s41416-020-0730-0 |
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author | Zhang, Qiang Ganapathy, Suthakar Avraham, Hava Nishioka, Takashi Chen, Changyan |
author_facet | Zhang, Qiang Ganapathy, Suthakar Avraham, Hava Nishioka, Takashi Chen, Changyan |
author_sort | Zhang, Qiang |
collection | PubMed |
description | BACKGROUND: Nicotine is a major tobacco component and found at circulating concentrations in smokers’ bloodstreams. Although considered a non-carcinogenic substance, nicotine rapidly defuses to tissues after being inhaled, inviting effects on cellular physiology, particularly in the lung. Widespread increased use of nicotine-based e-cigarettes, especially in younger adults, creates an urgent need for improved understanding of nicotine’s potential to impact human health. METHODS: Biological and biochemistry methods were used to interrogate the potential for nicotine to weaken the genetic integrity of murine and human-lung epithelial cells. RESULTS: We demonstrate that nicotine potentiates the growth of the lung epithelial cells in a dose–response fashion. Nicotine elicits an acute increase in reactive oxygen species (ROS), which persists at moderately high levels throughout the duration of nicotine exposure. The aberrant increases in ROS appear to induce ER stress and UPR activation, as reflected by BIP upregulation and PERK phosphorylation. Furthermore, prolonged nicotine exposure interferes with p53 function triggered by sodium arsenite. Unless p53 is suppressed, persistent nicotine exposure does not induce colony formation by lung epithelial cells in soft agar. CONCLUSION: The data suggest that nicotine treatment, by perturbing intracellular redox state and altering p53 function, can create a pro-tumorigenic environment in lung epithelium. The results suggest caution in using nicotine replacement therapies and e-cigarettes. |
format | Online Article Text |
id | pubmed-7078213 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-70782132021-01-31 Nicotine exposure potentiates lung tumorigenesis by perturbing cellular surveillance Zhang, Qiang Ganapathy, Suthakar Avraham, Hava Nishioka, Takashi Chen, Changyan Br J Cancer Article BACKGROUND: Nicotine is a major tobacco component and found at circulating concentrations in smokers’ bloodstreams. Although considered a non-carcinogenic substance, nicotine rapidly defuses to tissues after being inhaled, inviting effects on cellular physiology, particularly in the lung. Widespread increased use of nicotine-based e-cigarettes, especially in younger adults, creates an urgent need for improved understanding of nicotine’s potential to impact human health. METHODS: Biological and biochemistry methods were used to interrogate the potential for nicotine to weaken the genetic integrity of murine and human-lung epithelial cells. RESULTS: We demonstrate that nicotine potentiates the growth of the lung epithelial cells in a dose–response fashion. Nicotine elicits an acute increase in reactive oxygen species (ROS), which persists at moderately high levels throughout the duration of nicotine exposure. The aberrant increases in ROS appear to induce ER stress and UPR activation, as reflected by BIP upregulation and PERK phosphorylation. Furthermore, prolonged nicotine exposure interferes with p53 function triggered by sodium arsenite. Unless p53 is suppressed, persistent nicotine exposure does not induce colony formation by lung epithelial cells in soft agar. CONCLUSION: The data suggest that nicotine treatment, by perturbing intracellular redox state and altering p53 function, can create a pro-tumorigenic environment in lung epithelium. The results suggest caution in using nicotine replacement therapies and e-cigarettes. Nature Publishing Group UK 2020-01-31 2020-03-17 /pmc/articles/PMC7078213/ /pubmed/32001831 http://dx.doi.org/10.1038/s41416-020-0730-0 Text en © The Author(s), under exclusive licence to Cancer Research UK 2020 https://creativecommons.org/licenses/by/4.0/Note This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0). |
spellingShingle | Article Zhang, Qiang Ganapathy, Suthakar Avraham, Hava Nishioka, Takashi Chen, Changyan Nicotine exposure potentiates lung tumorigenesis by perturbing cellular surveillance |
title | Nicotine exposure potentiates lung tumorigenesis by perturbing cellular surveillance |
title_full | Nicotine exposure potentiates lung tumorigenesis by perturbing cellular surveillance |
title_fullStr | Nicotine exposure potentiates lung tumorigenesis by perturbing cellular surveillance |
title_full_unstemmed | Nicotine exposure potentiates lung tumorigenesis by perturbing cellular surveillance |
title_short | Nicotine exposure potentiates lung tumorigenesis by perturbing cellular surveillance |
title_sort | nicotine exposure potentiates lung tumorigenesis by perturbing cellular surveillance |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078213/ https://www.ncbi.nlm.nih.gov/pubmed/32001831 http://dx.doi.org/10.1038/s41416-020-0730-0 |
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