Presentations

      Inhalation Study For Cigarette-Smoke-Related Lung Tumorigenicity In A/J Mice

      Lichtner, R. B.; Friedrichs, B.; Büttner, A.; van Overveld, F.; Stinn, W.
      Conference date
      Mar 1, 2010
      Conference name
      Bioequivalence & Bioavailability 2010
      Link to more information
      Link to more information
      Topic
      Summary

      Cigarette smoking is a major cause of lung cancer; however, it has been difficult to reproduce the tumorigenicity of cigarette smoke in preclinical animal models. Increased lung tumorigenicity has been reported in A/J mice exposed for 5 months to an environmental tobacco smoke surrogate or to cigarette mainstream smoke (MS) followed by 4 months without further exposure. Here, we report on MS-induced lung tumor formation in male a/j mice after 18 months of exposure to a continuous flow of MS (6 h/day, 5 d/wk) at total particulate matter concentrations of 150 and 300 mg/m(3). Animal health, housing conditions, test atmosphere characterization, and markers for MS exposure (e.g., carboxyhemoglobin) were carefully monitored over the 18-month period to ensure the stability of the experimental conditions. Body weight gain was reduced dose-dependently in MS-exposed groups. An influx of neutrophils (up to 33% of leukocytes) and lymphocytes (up to 21%) into the bronchoalveolar space, indicating severe inflammation, was seen in MS-exposed groups. Classical histopathological evaluation of step-serial sections identified nodular alveolar hyperplasia, bronchiolo-alveolar adenoma, and carcinoma in all groups. Lung tumor multiplicity was increased in MS-exposed groups: up to 5-fold for adenomas and 2-fold for carcinomas. The data show that under these long-term, carefully controlled conditions, the A/J mouse is a promising model for cigarette-smoke-related lung tumorigenicity. 

      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.