title: Ara-C metabolism: implications for drug resistance and drug interactions.
abstract: Clinical studies of resistance to cytosine arabinoside have not produced agreement as to the specific biochemical lesions responsible for altered sensitivity, although experimental and clinical work supports the concept that a decreased ability to generate ara-CTP must be the ultimate effect of this lesion. 3-deazauridine, an inhibitor of CTP synthetase, was found to enhance ara-CTP production in murine tumor cells, and in the present study, was shown to inhibit deamination of ara-C at both the nucleoside and nucleotide level. Enhanced ara-CTP formation was observed in cells lacking cytidine deaminase (L1 210 and HL60), indicating that 3-deazauridine inhibition of deoxycytidylate deaminase may be important in this drug interaction.
mesh_terms: D015092:3-Deazauridine / Q000494:pharmacology; D000818:Animals; D003561:Cytarabine / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D003564:Cytidine Deaminase / Q000037:antagonists & inhibitors; D004347:Drug Interactions; D004351:Drug Resistance; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy; D013767:Tetrahydrouridine / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D003561:Cytarabine; D013767:Tetrahydrouridine; D015092:3-Deazauridine; D003564:Cytidine Deaminase