Cadmium and chromium induced oxidative stress and apoptopic cell death in cultured human chronic myelogenous leukemic k562 cells
Both sodium dichromate [Cr VI] and cadmium chloride [Cd II] are cytotoxic and mutagenic. This in vitro study focuses on the toxic and apoptopic potentials of these two cations on human K562 chronic myelogenous and HL-60 promyelocytic leukemic cells. The cells were incubated with 0-100 uM concentrations of these cations for 0, 24 and 48 hrs at 37°C. Cr VI and Cd II induced changes in intracelluar oxidized states of cells were detected using laser confocal microscopy. Cell cycle modulation and apoptosis of leukemic cells were determined by flow cytometry. Significant decreases in the G2/M phase were observed in the Cr VI and Cd II treated leukemic cells as compared to untreated cells. There was about 2.2- and 3.0-fold increases in DNA fragmentation (DF) in K562 cells following incubation with 12.5 and 25 uM Cr, respectively, while 1.2- and 1.7-fold increases in DF were observed with Cd II. Approximately 2.7- and 4.9-fold increases in cytochrome c. reduction (CCR) were observed following incubation with 12.5 and 25 u.M Cr VI, respectively, while approximately 1.6- and 3.3-fold increases in CCR were observed in K562 cells, demonstrating enhanced production of Superoxide anion. 3.1 to 6-fold increased hydroxyl radical production was observed following incubation of the K.562 cells with these cations at 12.5- and 25 uM. The extent of Cr induced apoptosis was significantly higher in K562 cells while Cd induced more apoptosis in HI-60 cells. These results were compared with similarly treated normal human peripheral blood mononuclear cells where there was no effect. The results demonstrate that both cations are toxic, producing oxidative tissue damage and apoptosis.
Joshi, S; Bagchi, D; Kuszvnski, C; Benner, EJ; Bagchi, M; Stohs, SJ
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