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PubMed1975

Cellular phosphorylation of 1-beta-D-arabinofuranosylcytosine 5-azacytidine with intact fibrosarcoma and leukemic cells.

The phosphorylation of 1-beta-D-arabinofuranosylcytosine (ara-C) and 5-azacytidine (5-aza-C) by A(T1)C1-3 hamster fibrosarcoma cells and L5178Y murine leukemic cells was studied, using intact cells. The cellular phosphorylation of both these nucleoside analogs appears to follow Michaelis-Menton kinetics. The apparent Km value for ara-C in the fibrosarcoma and leukemic cells was about 40 muM, whereas the apparent Km values for 5-aza-C in these cells were about 1.3 and 0.41 mM, respectively. Deoxycytidine and cytidine were found to be potent competitive inhibitors of the phosphorylation of ara-C and 5-aza-C, respectively, ara-C and 5-aza-C were found to be weak competitive inhibitors of the phosphorylation of deoxycytidine and cytidine, respectively. A clone isolated from the fibrosarcoma cells that was partially resistant to the cytotoxic effects of ara-C exhibited a higher Km value for both ara-C and deoxycytidine than the wild-type fibrosarcoma cells.

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