Sequential observation of 2,6-dimethylaniline-induced nasal lesions in a rat two-stage nasal carcinogenesis model after initiation with N-bis(2-hydroxypropyl) nitrosamine

Male F344 rats received diet containing 3,000 ppm 2,6-dimethylaniline (DMA) after initiation with a single subcutaneous injection of 2,400 mg/kg of N- bis(2-hydroxypropyl)nitrosamine (DHPN), and histological and electron micro scopic examinations of the nasal cavity were performed at 4, 13, 26 and 52 weeks to examine sequential changes induced by DMA. Severe atrophy of Bowma n's glands and epithelial disarrangement were apparent from week 3, followe d by dilatation and/or proliferation of Bowman's glands, degeneration of ep ithelial cells, and proliferation of undifferentiated epithelial cells from week 13. Focal glandular hyperplasias. dysplastic foci, and adenomas were observed from week 26, and carcinomas at 52 week. These nasal lesions were mostly evident in the olfactory mucosa in the nasal cavity, and their sever ity and/or incidences, other than atrophy of Bowman's glands, increased wit h the treatment period. Electron microscopically, carcinoma cells demonstra ted desmosomes, dense secretory granules identical to those in normal Bowma n's glands, a basement membrane, and microvilli. These results suggest that Bowman's glands are the target of DMA, giving rise to nasal carcinomas aft er DHPN-initiation.