Format

Send to

Choose Destination
Am J Respir Cell Mol Biol. 2018 Aug;59(2):179-188. doi: 10.1165/rcmb.2017-0375OC.

Intermittent Exposure to Cigarette Smoke Increases Lung Tumors and the Severity of Emphysema More than Continuous Exposure.

Author information

1
1 Division of Pulmonary Medicine, Department of Medicine, and.
2
2 Department of Pathology, Keio University, School of Medicine, Tokyo, Japan.

Abstract

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.

KEYWORDS:

M2 macrophage; cigarette smoke; emphysema; lung cancer

PMID:
29443539
DOI:
10.1165/rcmb.2017-0375OC

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center