Morphology of nasal cavity neoplasms in F344 rats after chronic feeding of p-cresidine, and intermediate of dyes and pigments.

p-Cresidine was administered in the feed at either of two concentrations (0.5 and 1.0 percent) to groups of 50 male and 50 female F344 rats for 104 weeks. Fifty animals of each sex were placed on test as controls and fed only the basic laboratory diet. All animals were observed for up to 2 weeks after discontinuation of treatment. In treated rats of both sexes, statistically significant numbers of adenomas, adenocarcinomas and squamous cell carcinomas were diagnosed in the nasal cavity. Most of the neoplasms were seen in the high dose male and female rats. 22 male rats (49%) showed poorly differentiated adenocarcinomas infiltrating the skull and brain. Only two male rats (4%) had a squamous cell carcinoma, whereas 8 female rats (17%) had squamous cell carcinomas and 14 female rats (30%) were diagnosed as having adenocarcinomas of the nasal cavity. In the 4 neoplasms studied ultrastructurally, features characteristic of adenocarcinomas were identified. Cells were arranged around central lumina lined with microvilli. The luminal edges of cells were linked together by junctional complexes. Cytoplasmic differentiation was generally poor, with ribosomes and polyribosomes being the predominant organelles. Neurogenic features were rare and difficult to identify due to unsatisfactory fixation. In one of the tumors, areas of squamous differentiation were found. The cells constituting such areas contained prominent bundles of tonofilaments which are characteristic of early squamous metaplasia.