Sequential Changes in Tumor Development Induced by 1,4-Dinitrosopiperazine in the Nasal Cavity of F344 Rats¹

Tumor development was examined sequentially in the nasal cavity of male F344 rats given 0.01 % 1,4-dinitrosopiperazine (DNP) in their drinking water for various periods. Rats were sacrificed at 10-week intervals for up to Week 50. On continuous DNP administration, simple hyperplasia of the nasal cavity epithelium was observed from Week 10, papillary hyperplasia, nodular hyperplasia, and papilloma was observed from Week 20, and carcinoma was observed from Week 30. Carcinoma was observed in 100% of the animals given DNP for 50 weeks. The carcinomas were adenocarcinomas (86%), adenosquamous cell carcinomas (10%), and undifferentiated carcinomas (4%). Simple hyperplasia was distributed evenly in the nasal cavity. Seventy % of the nodular hyperplasias and 81% of the carcinomas were located in the ethmoturbinate and about 75% of the papillary hyperplasias and papillomas were located in the nasoturbinate and maxilloturbinate. These findings suggest that nodular hyperplasia is very important as a precursor of carcinoma in the nasal cavity of rats treated with DNP and that papilloma is less important in relation to carcinoma development.