This research is directed at an examination of the effects of arabinosylcytosine (araC) and 5-azacytidine (5-azaC) on the synthesis and turnover of phospholipids, sialoglycolipids and sialoglycoproteins and the manifestation of these effects at both the cellular and membrane level.  The goal of this investigation is to further delineate the mode of action of these antineoplastic agents.  Current mechanisms for the cytotoxic action of these cytosine analogs implicate the phosphorylated intermediates ara-CTP and 5-aza-CTP as the active agents.  Since the synthesis of both phospholipid and sialylated membrane components and nucleic acid components require the formation CTP-activated intermediates, an effect on either the synthesis of these membrane components and thereby, membrane-related events, or on nucleic acid synthesis, and thereby nucleic acid-dependent events, is consistent with the widely-accepted hypothesis that araC and 5-azaC function as cytidine analogs.  These agents have been found to have significant effects on the synthesis of both these membrane components and on nucleic acid synthesis.  The significance of the membrane-related effects of araC and 5-azaC to the cytotoxicity of the drugs is of particular import since inhibition of nucleic acid synthesis alone has not been found to correlate with cell death.  More importantly, the potential for such agents to exert cytotoxic effects through effects on membrane synthesis and turnover should be explored since this information together with increasing knowledge of the membrane composition of normal and neoplastic cells, may provide a key to the selective use of these membrane-active agents in treatment of specific neoplasms.  The present research proposes to examine the effect of these agents on membrane synthesis by in vitro enzyme assays, as well as morphologically, by autoradiography and electron microscopy.