Overall oral health is believed to be determined to a great extent by both the quantity and the composition of saliva, and both of these factors are affected by drugs used in treating cancer patients. Further, it is not unusual for patients treated with certain chemotherapeutic drugs to exhibit oral problems such as dryness of the mouth, bleeding, infection, oral pain, difficulty in eating and stomatitis. The overall objective of this proposal is to determine the effects of several representative chemotherapeutic drugs on the functioning of salivary glands and on saliva produced by these glands. The ability of the glands to respond to physiological and pharmacological stimulation will be tested in anesthetized rats pretreated with these drugs and challenged with nerve stimulation, cholinergic (muscarinic) stimulation, or beta-adrenergic stimulation. In addition to measuring flow rate from these cannulated parotid and submaxillary glands, saliva collected in these experiments will be analyzed for its ionic, protein, and enzyme content as well as separated by electrophoresis. The above experiments will yield information on the effects of these drugs on saliva. The experiments outlined below are designed to determine where the drugs have an effect on the glands. Since the protein content of saliva is derived almost exclusively from secretory granules, granules will be isolated using centrifugation techniques and their contents analyzed to determine if the chemotherapeutic drugs have affected the cells in such a way that the granule contents are no longer an accurate reflection of the organic composition of saliva. Salivary glands will be fractionated to determine if there are changes in the activity of nonsecretory enzymes that might, for instance, be reflected in altered saliva electrolyte concentrations. The physiologic ability of the duct system to perform its normal passive and active transport processes will be ascertained using the perfused duct preparation.