Intermittent exposure to cigarette smoke increases lung tumors and the severity of emphysema more than continuous exposure

Naofumi Kameyama, Shotaro Chubachi, Ahmed E. Hegab, Hiroyuki Yasuda, Shizuko Kagawa, Akihiro Tsutsumi, Koichi Fukunaga, Masayuki Shimoda, Yae Kanai, Kenzo Soejima, Tomoko Betsuyaku

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


Lung cancer and chronic obstructive pulmonary disease are leading causes of morbidity and mortality worldwide, and cigarette smoking is a main risk factor for both. The presence of emphysema, an irreversible lung disease, further raises the risk of lung cancer in patients with chronic obstructive pulmonary disease. The mechanisms involved in smoke-induced tumorigenesis and emphysema are not fully understood, attributable to a lack of appropriate animal models. Here, we optimized a model of cigarette smoke (CS)–induced lung cancer and emphysema in A/J mice treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, a potent carcinogen. We investigated whether variations in CS exposure patterns with the same total amount and duration of exposure affect tumorigenesis and/or development of emphysema. Continuous CS exposure for 3 months significantly suppressed 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone–induced development of adenomas and adenocarcinomas; however, emphysema independently developed during this period. Surprisingly, intermittent CS exposure increased the severity of emphysema and resulted in a higher incidence of adenocarcinomas. Furthermore, intermittent CS exposure elicited a marked increase in M2-polarized macrophages within and near the developed tumors. By employing a CS exposure protocol with repeated cycles of cessation and relapse, we provide evidence that intermittent CS exposure enhances tumorigenesis and emphysema progression more than that of continuous CS exposure.

Original languageEnglish
Pages (from-to)179-188
Number of pages10
JournalAmerican journal of respiratory cell and molecular biology
Issue number2
Publication statusPublished - 2018 Aug


  • Cigarette smoke
  • Emphysema
  • Lung cancer
  • M2 macrophage

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


Dive into the research topics of 'Intermittent exposure to cigarette smoke increases lung tumors and the severity of emphysema more than continuous exposure'. Together they form a unique fingerprint.

Cite this