Ziram induces apoptosis and necrosis in human immune cells |
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Authors: | Qing Li Maiko Kobayashi Tomoyuki Kawada |
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Affiliation: | (1) Department of Hygiene and Public Health, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku Tokyo, 113-8602, Japan |
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Abstract: | Ziram as a dithiocarbamate fungicide is widely used throughout the world in agriculture and as an accelerating agent is used in latex production. In order to investigate ziram-induced apoptosis/necrosis and its underlying mechanism in human immune cells, a human monocyte-like cell line (U937) was treated with ziram at 0.0312–2 μM for 2–24 h at 37°C in a 5% CO2 incubator. Apoptosis/necrosis induced by ziram was determined by analysis of FITC-Annexin-V/PI staining and the intracellular level of active caspase-3 by flow cytometry and DNA fragmentation analysis. We found that ziram induced apoptosis/necrosis in U937 in a time- and dose-dependent manner, as shown by FITC-Annexin-V/PI staining. DNA fragmentation was detected when cells were treated with 0.5, 1, or 2 μM ziram for 24 h. Ziram also induced an increase in intracellular active caspase-3 in U937 cells in a dose-dependent manner, and a caspase-3 inhibitor, Z-DEVD-FMK, significantly inhibited the ziram-induced apoptosis. Moreover, it was found that ziram induced mitochondrial cytochrome c release in U937 cells. These findings indicate that ziram can induce apoptosis/necrosis in U937 cells, and this effect is partially mediated by activation of intracellular caspase-3 and mitochondrial cytochrome c release. |
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