Akademik Veri Yönetim Sistemi
LEUKEMIA, cilt.14, sa.1, ss.47-51, 2000 (SCI-Expanded, Scopus)
Inherent resistance of myeloblasts to vincristine (VCR) has been related to the activity of myeloperoxidase (MPO) which can degrade VCR in the presence of hydrogen peroxide (H2O2). We investigated the relationship between VCR degradation and hypochlorous acid (HOCI) generation from the reaction of H2O2 with chlorine (CI) as catalyzed by MPG. A cell-free system, three human leukemia cell lines (CEM/CCRF, HL-60, U937) and 15 bone marrow samples from children with acute myeloid leukemia (AML) were studied. VCR cytotoxicity was evaluated by MTT assay and by quantitative measurement of apoptosis. In vitro levels of VCR in cell-free systems were measured by high performance liquid chromatography (HPLC), and intracellular HOCI levels by oxidation of 5-thio-2-nitrobenzoic acid with the accompanying decrease in the absorbency at 412 nm. VCR was degraded by increasing concentrations of HOCI in cell-free systems and this activity was inhibited by taurine, which is known to block HOCI activity. This finding was confirmed by the VCR cytotoxicity studies on cell lines. The HOCI-producing myeloblasts from patients were resistant to VCR. In five samples out of eight HOCI was also detected extracellularly. These results suggest that oxidation by HOCI may be the final step in VCR degradation catalyzed by MPO through its action on intracellular H2O2 and CI.