Nicotine exposure potentiates lung tumorigenesis by perturbing cellular surveillance

Qiang Zhang, Suthakar Ganapathy, Hava Avraham, Takashi Nishioka, Changyan Chen

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)904-911
Number of pages8
JournalBritish Journal of Cancer
Issue number6
Publication statusPublished - 2020 Mar 17


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