Comparative ultrastructure of submaxillary salivary glands from mice treated with cytosine arabinoside, cyclocytidine, and anhydro-ara-5-fluorocytidine.

The effects of cytosine arabinoside (ara-C), cyclocytidine (cyclo-C), and anhydro-ara-5-fluorocytidine (AAFC) on the ultrastructure of the serous and mucous cells of the submaxillary salivary glands were evaluated in normal BDF1 mice. Rapid loss of zymogen granules from serous cells and a discharge of mucous cell contents were observed within the first hour after administration of a single iv dose of cyclo-C. Serous cells were essentially devoid of granules (1-3 mum) within 3 hours; regranulation observed initially at 6 hours produced a population of microgranules (approximately 0.8 mum) by 24 hours; most serous cells contained a reduced complement of small granules through 96 hours after cyclo-C. Mucous cells recovered secretory content within 3-6 hours after drug administration. Neither ara-C nor AAFC produced zymogen-granule or mucous discharge or other cytopathologic effects in the murine submaxillary salivary glands. Thus, it can be postulated that cyclo-C itself is the secretogogue. The ultrastructural changes observed in this study provide a cytopathologic correlate of the salivary gland dysfunctions reported to follow the administration of cyclo-C to man.