Hydroxyurea (HU) increases activation of 2',3'-dideoxycytidine (ddC) (Meeting abstract).

Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.

Hydroxyurea (HU) increases activation of 2',3'-dideoxycytidine (ddC) (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 36:A2410 1995. Unique Identifier : AIDSLINE ICDB/95610184
Agarwal RP; He J; Bansal M; Gupta V; Medical Oncology (R-71), Univ. of Miami School of Medicine,; Miami, FL 33136

Abstract: 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.

Keywords: Biotransformation Cell Division/DRUG EFFECTS Cell Line Human Hydroxyurea/*PHARMACOLOGY HIV/*DRUG EFFECTS Virus Replication/*DRUG EFFECTS Zalcitabine/PHARMACOLOGY/*PHARMACOKINETICS ABSTRACT
951030
M95A0969

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