title: 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.
authors.affiliation: Department of Hygiene and Public Health, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan. qing-li@nms.ac.jp
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Maiko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kawada
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D005434:Flow Cytometry; D005659:Fungicides, Industrial / Q000633:toxicity*; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009336:Necrosis / Q000139:chemically induced; D020298:U937 Cells; D015039:Ziram / Q000633:toxicity*
chemical_list: D005659:Fungicides, Industrial; D015039:Ziram; D045304:Cytochromes c