INCREASED ACTIVATION OF 1-BETA-D-ARABINOFURANOSYLCYTOSINE BY HYDROXYUREA IN L1210 CELLS

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  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (9) , 3286-3292
Abstract
Hydroxyurea (0.1-10 mM), incubated with L1210 [mouse leukemia] cells in the presence of 1 .mu.M 1-.beta.-D-arabinofuranosylcytosine (ara-C), produced a concentration- and time-dependent increase in levels of 1-.beta.-D-arabinofuranosylcytosine 5''-triphosphate (ara-CTP). This effect was abolished upon removal of hydroxyurea from cells. The enhancement of ara-CTP by hydroxyurea was observed for concentrations of ara-C ranging from 0.1-100 .mu.M. These changes were not associated with alteration in the activity of deoxycytidine kinase, measured in extracts from L1210 cells with and deoxycytidine triphosphate. Hydroxyurea increased the apparent maximum velocity of this enzyme when determined with intact cell preparations, a finding consistent with alteration in endogenous regulation of this enzyme. A 4-h i.v. infusion of hydroxyurea (192 mg/kg per h) with ara-C (1 mg/kg per h) into ascites tumor-bearing mice increased L1210 cell concentrations of ara-CTP. ara-C levels in plasma and L1210 cells were unaffected by hydroxyurea. The enhancement of ara-CTP concentration in vivo, like in vitro, resulted from changes in ara-C conversion in the L1210 cells.