Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice

Proc Natl Acad Sci U S A. 2019 Oct 22;116(43):21727-21731. doi: 10.1073/pnas.1911321116. Epub 2019 Oct 7.

Abstract

Electronic-cigarettes (E-cigs) are marketed as a safe alternative to tobacco to deliver the stimulant nicotine, and their use is gaining in popularity, particularly among the younger population. We recently showed that mice exposed to short-term (12 wk) E-cig smoke (ECS) sustained extensive DNA damage in lungs, heart, and bladder mucosa and diminished DNA repair in lungs. Nicotine and its nitrosation product, nicotine-derived nitrosamine ketone, cause the same deleterious effects in human lung epithelial and bladder urothelial cells. These findings raise the possibility that ECS is a lung and bladder carcinogen in addition to nicotine. Given the fact that E-cig use has become popular in the past decade, epidemiological data on the relationship between ECS and human cancer may not be known for a decade to come. In this study, the carcinogenicity of ECS was tested in mice. We found that mice exposed to ECS for 54 wk developed lung adenocarcinomas (9 of 40 mice, 22.5%) and bladder urothelial hyperplasia (23 of 40 mice, 57.5%). These lesions were extremely rare in mice exposed to vehicle control or filtered air. Current observations that ECS induces lung adenocarcinomas and bladder urothelial hyperplasia, combined with our previous findings that ECS induces DNA damage in the lungs and bladder and inhibits DNA repair in lung tissues, implicate ECS as a lung and potential bladder carcinogen in mice. While it is well established that tobacco smoke poses a huge threat to human health, whether ECS poses any threat to humans is not yet known and warrants careful investigation.

Keywords: DNA damage; DNA repair; bladder hyperplasia; electronic-cigarette; lung cancer.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma of Lung / chemically induced*
  • Adenocarcinoma of Lung / pathology
  • Animals
  • DNA Damage / drug effects
  • DNA Repair / drug effects
  • Electronic Nicotine Delivery Systems*
  • Hyperplasia / chemically induced*
  • Hyperplasia / pathology
  • Lung / pathology
  • Lung Neoplasms / chemically induced*
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Nicotine / administration & dosage
  • Smoke / adverse effects*
  • Smoking / adverse effects*
  • Urinary Bladder / pathology
  • Urothelium / pathology

Substances

  • Smoke
  • Nicotine