Posters

      Towards A Mouse Inhalation Model For Cigarette-Smoke-Induced Lung Tumorigenesis

      Stinn, W.; Buettner, A.; Friedrichs, B.; Luetjen, S.; Gebel, S.; Lichtner, R. B.; van Overveld, F.; H-Haussmann, H-J. Haussmann.
      Conference date
      Nov 9, 2008
      Conference name
      American College of Toxicology (ACT) 2008
      Link to more information
      Topic
      Summary

      A laboratory animal model for cigarette-smoke-induced pulmonary tumorigenesis is needed to unravel mechanistic and etiologic aspects of the disease, to investigate chemopreventive and early diagnostic means, and to evaluate risks from novel tobacco products. Here, we show the first reproducible series of studies using cigarette mainstream smoke (MS) inhalation in mice (whole-body, 6 h/d, 5 d/w). Male A/J mice exposed to up to 300 mg/m(3) total particulate matter for 18 months showed dose-dependent increases in the multiplicity of pulmonary adenomas (up to 5-fold) and adenocarcinomas (up to 2-fold). With shorter inhalation periods (5 or 10 months), increases in tumor multiplicity were seen only when the inhalation was followed by post-exposure periods (4 to 13 months; maximum overall duration of studies: 18 months). Lung tumor multiplicity was also increased in male Swiss SWR mice after 5 months of inhalation followed by a 4-month post-exposure period. For both A/J and Swiss mice, the tumorigenic potential was associated mainly with the MS particulate rather than the vapor phase. Tumorigenesis in A/J mice was associated with inflammatory processes indicated by changes in gene expression in lung tissue as well as increased molecular and cellular markers in the bronchoalveolar lavage fluid. Some of these changes reversed during post-exposure. Thus, chronic MS inhalation reproducibly increased lung tumorigenesis in A/J mice under conditions which allow the full development of the tumorigenic potential. Further investigations are needed to qualify the biological relevance of the model. 

      PMIScience.com is operated by Philip Morris International for the purpose of publishing and disseminating scientific information about Philip Morris International’s efforts in support of its smoke-free product portfolio. This site is a global site for use by scientists, the public health and regulatory communities, and other stakeholders with an interest in tobacco policy. The purpose of this site is not advertising or marketing, nor is it directed at any specific market. It is not intended for use by consumers. New tobacco products sold in the United States are subject to FDA regulation; therefore the content of this site is not intended to make, and nor should it be construed as making, any product related claims in the United States without proper FDA authorization. ​
      ​
      Reduced Risk Products ("RRPs”) is the term we use to refer to products that present, are likely to present, or have the potential to present less risk of harm to smokers who switch to these products versus continuing smoking. PMI has a range of RRPs in various stages of development, scientific assessment and commercialization. All of our RRPs are smoke-free products that deliver nicotine with far lower quantities of harmful and potentially harmful constituents than found in cigarette smoke.