Inhaled carcinogen-induced lung cancer originates at the bronchial epithelium. Traditional animal models with tumor grafting or intraperitoneal/intravenous injection of tobacco carcinogens either lack the natural stages of tumor initiation and progression, or lack the advantage of modeling the disease through direct exposure of the airway epithelium to the causative agents. To overcome these problems, we used intratracheal inoculation of the major tobacco carcinogens benzo[a]pyrene (BP) and nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) to induce lung premalignancy and lung cancer in two different strains of mice. This mouse model of inhaled carcinogen-induced lung cancer consistently mimics the carcinogenesis process in tobacco-induced human lung cancer that progresses through a series of identifiable histopathological stages. In our model the lung carcinogenesis clearly progresses through three different stages: 1. Early transitional stage with no pathological lesions (0-15 weeks after first dose of the carcinogens); 2. Premalignant stage with dysplasia in the lungs in 100% of both A/J and ICR mice at 16 weeks after the first dose of the carcinogens; 3. Malignant stage with tumor nodules developed in the lungs in 100% of A/J and > 60% of ICR mice at 20-24 weeks. We have been using this model in trying to identify key molecular players in each stage that could possibly serve as therapeutic targets for lung cancer treatment. Currently it is one of best available models for studying environmental carcinogen-induced lung cancer and warrants further characterization. Future studies using this model are expected to enhance our understanding of the disease and facilitate our efforts of developing early therapeutic interventions. Supported by NIH grants CA96515 and CA104297.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3472.