Cadmium- and chromium-induced oxidative stress, DNA damage, and apoptotic cell death in cultured human chronic myelogenous leukemic K562 cells, promyelocytic leukemic HL-60 cells, and normal human peripheral blood mononuclear cells
✍ Scribed by D. Bagchi; S. S. Joshi; M. Bagchi; J. Balmoori; E. J. Benner; C. A. Kuszynski; S. J. Stohs
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 178 KB
- Volume
- 14
- Category
- Article
- ISSN
- 1095-6670
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✦ Synopsis
Sodium dichromate [Cr(VI)] and cadmium chloride [Cd(II)] are both cytotoxic and mutagenic. This study examined the toxic and apoptotic potentials of these two cations on three cell types in vitro, namely, human chronic myelogenous leukemic (CML) K562 cells, promyelocytic leukemic HL-60 cells, and normal human peripheral blood mononuclear cells. The cells were incubated with 0-100 lM concentrations of the two cations for 0, 24, or 48 hours at 37ЊC. Both Cr(VI) and Cd(II) induced changes in intracellular oxidized states of cells, which were detected using laser scanning confocal microscopy. Cell cycle modulation and apoptosis of the K562 cells by Cr(VI) and Cd(II) were determined by flow cytometry. Significant decreases in the G2/M phase were observed in the Cr(VI) and Cd(II) treated CML cells compared with untreated cells. At 12.5 lM, Cr(VI) induced greater apoptosis in K562 cells as compared with Cd(II). In the K562 cells, 2.2-and 3.0-fold increases in DNA fragmentation were observed following incubation with 12.5 and 25 lM Cr(VI), respectively, and 1.2-and 1.7-fold increases in DNA fragmentation were observed with Cd(II). Furthermore, approximately 2.7-and 4.9-fold increases in cytochrome c reduction were observed following incubation with 12.5 and 25 lM Cr(VI), respectively, and 1.6-and 3.3-fold increases in cytochrome c reduction were observed with Cd(II), demonstrating enhanced production of superoxide anion. Approximately 3.1 to 6-fold increases in hydroxyl radical production were observed following incubation of the K562 cells with