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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Acknowledgments
This work was supported by a grant from the Ministry of Education, Culture, Sports, Science and Technology. We are grateful to the staff at the Department of Hygiene and Public Health, Nippon Medical School for their assistances.
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Li, Q., Kobayashi, M. & Kawada, T. Ziram induces apoptosis and necrosis in human immune cells. Arch Toxicol 85, 355–361 (2011). https://doi.org/10.1007/s00204-010-0586-9
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DOI: https://doi.org/10.1007/s00204-010-0586-9