Morphogenesis of nasal tumors in rats exposed to hexamethylphosphoramide by inhalation

Nasal tumors were induced in rats by inhalation exposure to hexamethylphosphoramide (HMPA) for 6 to 24 months at concentrations of 50, 100, 400, and 4000 parts per billion (ppb), but not in rats exposed at 10 ppb for 24 months. Most nasal tumors were epidermoid carcinomas and developed from the respiratory epithelium or subepithelial nasal gland, both of which revealed squamous metaplasia or dysplasia in the anterior nasal cavity. The glandular cells appear to play an important role in developing epidermoid carcinomas in the nasal cavity. The ultrastructure of epidermoid carcinomas revealed abundant features of glandular differentiation in the neoplastic squamous cells. The morphological expression of glandular cell metamorphosis in the epidermoid carcinoma included intermediate cells showing both glandular and squamous differentiation, inter- or intracellular lumina, secretory vesicles, and mucus droplets in squamous cells and keratin plates.