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  • Title: Ara-C metabolism: implications for drug resistance and drug interactions.
    Author: Chabner BA, Hande KR, Drake JC.
    Journal: Bull Cancer; 1979; 66(1):89-92. PubMed ID: 420952.
    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.
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