CYTOTOXIC SYNERGISM BETWEEN HYDROXYUREA (HU) AND 3'-AZIDO 3'-DEOXYTHYMIDINE (AZT) IN CHRONIC MYELOID LEUKEMIA (CML) MODELS (MEETING ABSTRACT) NLM AIDSLINE Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.

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CYTOTOXIC SYNERGISM BETWEEN HYDROXYUREA (HU) AND 3'-AZIDO 3'-DEOXYTHYMIDINE (AZT) IN CHRONIC MYELOID LEUKEMIA (CML) MODELS (MEETING ABSTRACT)

Proc Annu Meet Am Assoc Cancer Res; 33:A2628 1992. Unique Identifier : AIDSLINE ICDB/92685157
Tosi P; Tura S; Visani G; Inst. of Hematology 'Seragnoli,' Bologna, Italy

Abstract: It has been previously reported that de novo thymidylate synthesis inhibitors, such as fluorouracil and methotrexate, enhance AZT antineoplastic activity. In this study, we aim to demonstrate that a reduction in deoxyribonucleotide pools caused by HU could potentiate AZT cytotoxicity. In 2 CML cell lines, K562 and RWLeu4, the IC50 of HU is decreased by 40% and 51.5%, respectively, after 72-hr coincubation with AZT. [3H]AZT incorporation into cellular DNA, as assayed by DNaseI hydrolysis, is increased by 42% in K562 and 71% in RWLeu4 when HU is added. Preliminary results on clonogenicity of fresh CML GM-CFU from patients confirm an increased activity of the combination vs the 2 drugs alone. Isobologram analysis of the data shows a synergistic effect of the 2 drugs. This combination deserves further testing in vivo in CML models resistant to the conventional HU or 6MP + HU regimens.
Keywords: Cell Survival/*DRUG EFFECTS Deoxyribonucleotides/METABOLISM Drug Synergism Human Hydroxyurea/*PHARMACOLOGY Kinetics Leukemia, Myeloid, Chronic Tumor Stem Cell Assay Zidovudine/*PHARMACOLOGY ABSTRACT

KWDcellsurvival/KWDdrugeffectsdeoxyribonucleotides/metabolismdrugsynergismhumanhydroxyurea/KWDpharmacologykineticsleukemia,myeloid,chronictumorstemcellassayzidovudine/KWDpharmacologyabstract
921130
M92B0884

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