N-Nitrosopiperidine (CAS: 100-75-4) and 2,6-dimethylnitrosomorpholine induced
tumors of the olfactory epithelium in white Wistar rats. Some
tumors were serially transplanted to NMRI nude mice (nu/nu) and passaged up to 16 times in a 1-year period.
Tumor tissues from rats and mice were analyzed by conventional pathological stains, by electron microscopy, and by immunofluorescence microscopy with the use of
antibodies specific for different intermediate filaments. Both
carcinogens induced
tumors built of undifferentiated small, round cells in which neuroblastic (Homer-Wright) rosettes and ependymal (Flexner) rosettes were visible. In some
tumors areas of squamous cell
metaplasia could be observed, which sometimes differentiated toward
squamous cell carcinoma. Electron microscopy showed neurosecretory granules in some
tumor cells, and biochemical studies of plasma showed in some instances elevated
ACTH and
calcitonin levels. Intermediate filament typing showed that in general the undifferentiated
tumor cells lack intermediate filaments, although in 6 of 29
tumors a few cells that stained positively for neurofilaments were found. Flexner rosettes, the areas showing squamous cell differentiation, and occasional single
tumor cells were positive with
keratin antibodies. Neurofilament expression was observed in a minor population of
tumor cells placed in tissue culture. These findings are used to argue that the chemically induced rat
tumors are a model for human esthesioneuroepithelioma and furthermore that the light basal cells of the epithelium may be the stem cells of the rat
tumors as well as of its rare counterparts in humans.