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.