Cellular changes induced by the tobacco-specific carcinogen 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone in the respiratory tract of Syrian golden hamsters.

The N-nitrosamine 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK) is abundant in cigarette smoke and is a potent pulmonary carcinogen in Syrian golden hamsters. After intratracheal instillation of NNK to Syrian golden hamsters, we observed focal cell death in the trachea and bronchi followed by cellular regeneration. Regenerating cells were not ciliated and led to mucous-cell hyperplasia followed by squamous-cell metaplasia. Lung alterations consisted of bronchiolar hyperplasia with severe dysplastic changes in association with interstitial pneumonitis. NNK induces preneoplastic cellular changes similar to those observed in the pulmonary epithelium of smokers.