Ziram induces apoptosis and necrosis in human immune cells

Arch Toxicol. 2011 Apr;85(4):355-61. doi: 10.1007/s00204-010-0586-9. Epub 2010 Sep 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Cell Survival / drug effects
  • Cytochromes c / metabolism
  • DNA Fragmentation
  • Flow Cytometry
  • Fungicides, Industrial / toxicity*
  • Humans
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • Monocytes / pathology
  • Necrosis / chemically induced
  • U937 Cells
  • Ziram / toxicity*

Substances

  • Fungicides, Industrial
  • Ziram
  • Cytochromes c