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Ziram induces apoptosis and necrosis in human immune cells.

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.
AuthorsQing Li, Maiko Kobayashi, Tomoyuki Kawada
JournalArchives of toxicology (Arch Toxicol) Vol. 85 Issue 4 Pg. 355-61 (Apr 2011) ISSN: 1432-0738 [Electronic] Germany
PMID20842346 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Fungicides, Industrial
  • Ziram
  • Cytochromes c
Topics
  • Apoptosis (drug effects)
  • Cell Survival (drug effects)
  • Cytochromes c (metabolism)
  • DNA Fragmentation
  • Flow Cytometry
  • Fungicides, Industrial (toxicity)
  • Humans
  • Monocytes (drug effects, metabolism, pathology)
  • Necrosis (chemically induced)
  • U937 Cells
  • Ziram (toxicity)

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