The Utility of N-nitrosamines as Initiators for a 26-Week Rat Two-Stage Nasal Carcinogenesis Model

To examine the utility of N-nitrosamines as initiators for a 26-week two-stage rat nasal carcinogenesis model, male F344 rats were treated with 2,6-dimethylaniline (DMA), possessing promoting potential for the rat nasal cavity, after initiation with 3 subcutaneous injections of 1500 mg/kg of N-bis(2-hydroxypropyl)nitrosamine (DHPN), 30 mg/kg of N-nitrosobis(2-oxypropyl)amine (BOP), or 30 mg/kg of N-nitrosopiperidine (NPIP). Histopathologically diagnosed nasal epithelial hyperplasias and tumors, including carcinomas, were induced with all three, with significant increase in the DHPN+DMA, BOP+DMA, and NPIP+DMA groups compared with the DHPN alone, BOP alone, and NPIP alone groups, respectively. These results strongly suggested that repeated subcutaneous injections of DHPN, BOP, or NPIP are useful for initiation in the present 26-week nasal carcinogenesis model.