Document 0968
 DOCN  M95A0968
 TI    Hydroxyurea (HU) increases activation of 2',3'-dideoxycytidine (ddC)
       (Meeting abstract).
 DT    9510
 AU    Agarwal RP; He J; Bansal M; Gupta V; Medical Oncology (R-71), Univ. of
       Miami School of Medicine,; Miami, FL 33136
 SO    Proc Annu Meet Am Assoc Cancer Res; 36:A2410 1995. Unique Identifier :
       AIDSLINE ICDB/95610184
 AB    ddC, one of the most potent inhibitors of HIV replication, exerts its
       anti-HIV effect through its 5'-triphosphate, ddCTP. We have examined the
       effect of HU on ddCTP formation from ddC. Following incubation of H9
       cells (human lymphocytic cell line) with 500 uM HU and 25 uM ddC for 24
       hr, cell count, cellular DNA content, and ddC nucleotide levels were
       determined. HU arrested the cells in G1 phase, inhibited cell growth to
       49%, and increased ddC incorporation to 232.3 +/- 61.9% of control. The
       increase in ddCTP formation was HU concentration dependent, ie, 171%,
       230%, 319%, and 361% of control in 10, 50, 100, and 500 uM HU treated
       cells, respectively. 2'-Deoxycytidine almost completely abolished the
       formation of ddCTP to 0-4.4% of control. The use of HU in combination of
       ddC may enhance the effectiveness of ddC.
 DE    Biotransformation  Cell Division/DRUG EFFECTS  Cell Line  HIV/*DRUG
       EFFECTS  Human  Hydroxyurea/*PHARMACOLOGY  Virus Replication/*DRUG
       EFFECTS  Zalcitabine/PHARMACOLOGY/*PHARMACOKINETICS  MEETING ABSTRACT

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