Effects of minute amounts of cigarette smoke with or without nebulized N-nitroso-N-methylurethane on the respiratory tract of mice.

The effects of minute amounts of cigarette smoke with or without nebulized N-nitroso-N-methylurethane (NMUT) on the respiratory epithelia of mice were examined. The first group received the combination of NMUT nebulization and cigarette smoke inhalation, the second group NMUT nebulization only, the third group cigarette smoke inhalation only and the fourth group no treatment. The first group showed squamous cell carcinomas in the nasal cavity (4 out of 10 mice), trachea (4 out of 10 mice) and lung (2 out of 10 mice). In the second group squamous cell carcinomas with keratosis were found in the nasal cavity (2 out of 10 mice) and in the lung (1 out of 10 mice). Furthermore, basal cell hyperplasias, squamous metaplasias and dysplastic changes were found in these two groups. The third group showed basal cell hyperplasias and squamous metaplasias in the nasal cavity and hypertrophy of Clara cells. No marked changes of epithelia of the respiratory tract in the fourth group were seen. Adenomas and adenocarcinomas were not found in any group. Statistically, there is a significant difference in the incidence of dysplastic change of the trachea between group 1 and group 2 (P less than 0.05). These results suggest that minute amounts of cigarette smoke, in combination with carcinogens, may have cocarcinogenic action and that squamous cell carcinoma may pass through the course of basal cell hyperplasia, squamous metaplasia and dysplastic change of the epithelia.