Induction of preneoplastic and neoplastic lesions in grafted rat tracheas continuously exposed to benzo(a)pyrene.

Heterotopically transplanted rat tracheas were continuously exposed to measured amounts of benzo(a)pyrene over a period of 1 to 6 months. The cumulative doses ranged from 10 to 2490 microng. The morphological response of the tracheal epithelium was characterized by hyperplasis during the first 2 weeks, followed by atrophy. Squamous metaplasias did not appear until after 4 months of exposure; at 4 and 6 months numerous dysplastic lesions and noninvasive carcinomas resembling those seen in the airways of humans were found in the higher carcinogen dose groups. The first invasive carcinomas developed at 4 months in the groups given 1250 microng or more benzo(a)pyrene. The lowest dose tested that produced a carcinoma within the observation period of 22 months was 300 microng benzo(a)pyrene. The majority of the neoplasms were squamous cell carcinomas, although several adenocarcinomas and sarcomas also developed. Since a variety of metaplastic and dyplastic lesions can be induced by carcinogenic polycyclic hydrocarbons in the transplanted rat tracheas, this experimental model appears to be well suited for the study of the sequential epithelial changes that lead to respiratory tract neoplasia.