In human lymphocytes, the antiviral nucleoside 2', 3'-dideoxycytidine undergoes substantial anabolism but negligible catabolism. Using tritiated drug and authentic standards as markers, the mono, di and triphosphate forms of the compound have been identified in human, murine and caprine cells exposed to 1MuM nucleoside for twenty-four hours. In ATH8 cells, the concentration of dideoxycytidine-5-triphosphate reached under these conditions approximated 0.5Mum, a level capable of inhibiting retroviral reverse transcriptase, presumably by a chain-terminating mechanism. A fourth metabolite with unique chromatographic behavior was also identified. Because this metabolite resisted attack by alkaline phosphatase but was decomposed by venom phosphodiesterase, it was concluded to be a phosphodiester; because it incorporated label from (14C) choline as well as from (3H) dideoxycytidine, it is postulated to be dideoxycytidine diphosphocholine. In studies of the catabolism of dideoxycytidine, no deamination of the nucleoside nor of its 5'-monophosphate could be demonstrated with murine enzymes; however, activities contaminating bacterial phosphorylases did slowly deaminate the drug.
