A further review of inhalation studies with cigarette smoke and lung cancer in experimental animals, including transgenic mice

Context: The lack of an effective animal model for pulmonary carcinogenesis in smokers is a continuing problem for researchers trying to design Potentially Reduced Risk Products for those smokers who are either unwilling or unable to quit smoking. The major failing of inhalation assays with cigarette smoke in laboratory animals is that these assays produce only small percentages of animals with pulmonary tumors (e. g. adenomas, with the occasional adenocarcinoma), as opposed to the highly invasive carcinomas (e. g. small cell and squamous cell) seen in smokers. Objective: To update previous reviews on animal models, and to add different types of transgenic (Tg) mice to the review. Methods: Reviews were made of articles retrieved from PubMed and elsewhere. Results: The addition of Tg mice to the arsenal of tests used for the evaluation of the carcinogenic potential of cigarettes did not result in any better understanding of the inability of such testing to reflect the epidemiological evidence for lung cancer in smokers. Conclusion: As in previous reviews on the subject, the best assay providing support for the epidemiology data is still the 5-month whole-body exposure of male A/J mice to a combination of mainstream/sidestream smoke, followed by a 4-month recovery.