Journal Article

Lung Inflammatory Effects, Tumorigenesis, and Emphysema Development in a Long-Term Inhalation Study with Cigarette Mainstream Smoke in Mice

Walter Stinn, Ansgar Buettner, Horst Weiler, Baerbel Friedrichs, Sonja Luetjen, Frans van Overveld, Kris Meurrens, Kris Janssens, Stephan Gebel, Regina Stabbert and Hans-Juergen Haussmann

in Toxicological Sciences

Volume 131, issue 2, pages 596-611
Published in print February 2013 | ISSN: 1096-6080
Published online October 2012 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfs312

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Cigarette smoking is the leading cause of lung cancer and chronic obstructive pulmonary disease, yet there is little mechanistic information available in the literature. To improve this, laboratory models for cigarette mainstream smoke (MS) inhalation–induced chronic disease development are needed. The current study investigated the effects of exposing male A/J mice to MS (6h/day, 5 days/week at 150 and 300mg total particulate matter per cubic meter) for 2.5, 5, 10, and 18 months in selected combinations with postinhalation periods of 0, 4, 8, and 13 months. Histopathological examination of step-serial sections of the lungs revealed nodular hyperplasia of the alveolar epithelium and bronchioloalveolar adenoma and adenocarcinoma. At 18 months, lung tumors were found to be enhanced concentration dependently (up to threefold beyond sham exposure), irrespective of whether MS inhalation had been performed for the complete study duration or was interrupted after 5 or 10 months and followed by postinhalation periods. Morphometric analysis revealed an increase in the extent of emphysematous changes after 5 months of MS inhalation, which did not significantly change over the following 13 months of study duration, irrespective of whether MS exposure was continued or not. These changes were found to be accompanied by a complex pattern of transient and sustained pulmonary inflammatory changes that may contribute to the observed pathogeneses. Data from this study suggest that the A/J mouse model holds considerable promise as a relevant model for investigating smoking-related emphysema and adenocarcinoma development.

Keywords: lung tumorigenesis; pulmonary emphysema; lung inflammation; cigarette mainstream smoke; inhalation; A/J mice

Journal Article.  12058 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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