Mitoxantrone-induced DNA damage in leukemia cells is enhanced by treatment with high-dose arabinosylcytosine.

作者: Volker Heinemann , David Murray , Ronald Walters , Raymond E. Meyn , William Plunkett

DOI: 10.1007/BF00273412

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摘要: In a phase II study, patients with chronic myelogenous leukemia in blast crisis (CML-BC) were treated intravenous (IV) mitoxantrone (5 mg/m2) per day given over 30 min x 5 days and high-dose arabinosylcytosine (ara-C) (3 g/m2 IV q 12 h 6).The effect of this treatment on DNA damage was studied the cells four using alkaline elution technique modified to measure unlabeled human cells. A fluorescence assay Hoechst 33258 dye applied for determination eluted DNA.After single infusion mitoxantrone, neither frank nor protein-associated single-strand breaks (SSB) observed.Even repeated 3 consecutive did not induce significant SSB. However, after combined sequential ara-C pattern changed, showing damage.SSB remained apparent 24 increased subsequent doses mitoxantrone. Studies other alone reveal SSB (n=5).Following median peak concentrations intracellular ara-CTP (the triphosphate ara-C) exceeded 900 μM,a value greater than that observed CML-BC receiving (230 μM, n=15, P<0.02). The present study shows applicability method vivo. enhanced suggests synergistic drug effect.

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