Effects of carcinogen dose on the characteristics of the tracheal tumor response induced by N-nitroso-N-methylurea in hamsters.

Tracheal tumors were induced by repeated intratracheal exposures to the carcinogen N-nitroso-N-methylurea (NMU), using a catheter system previously described. Carcinogen concentrations of 0.25, 0.50 and 1.0% were employed in 20 or 30 twice-weekly exposures. Most of the tumors developed in the mid-portion of the tracheas. Virtually all tumors developed after the end of the 10- to 15-week exposure period. Tumor incidence ranged from 20-94% with mean tumor induction times of 13-46 weeks, depending on NMU concentration and frequency of exposure (i.e., dose). At lower doses, mostly non-invasive tumors were induced; at higher doses, mostly invasive carcinomas of various histological types (epidermoid, adeno-, epidermoid-adeno, and anaplastic large- and small-cell carcinomas) were induced. Adenocarcinomas were most frequent at low NMU concentrations. The possible mechanisms of the carcinogen dose effects are discussed.