caa a22 4500 445853670 CHVBK 20180317145421.0 cr unu---uuuuu 170323e20110401xx s 000 0 eng 10.1007/s00204-010-0586-9 doi (NATIONALLICENCE)springer-10.1007/s00204-010-0586-9 Ziram induces apoptosis and necrosis in human immune cells [Elektronische Daten] [Qing Li, Maiko Kobayashi, Tomoyuki Kawada] 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 0.0312-2μM for 2-24h 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 2μM ziram for 24h. 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. Springer-Verlag, 2010 Annexin-V nationallicence Apoptosis nationallicence Caspase-3 nationallicence Cytochrome c nationallicence DNA fragmentation nationallicence Necrosis nationallicence U937 nationallicence Ziram nationallicence Li Qing Department of Hygiene and Public Health, Nippon Medical School, 1-1-5 Sendagi, 113-8602, Bunkyo-ku, Tokyo, Japan aut Kobayashi Maiko Department of Hygiene and Public Health, Nippon Medical School, 1-1-5 Sendagi, 113-8602, Bunkyo-ku, Tokyo, Japan aut Kawada Tomoyuki Department of Hygiene and Public Health, Nippon Medical School, 1-1-5 Sendagi, 113-8602, Bunkyo-ku, Tokyo, Japan aut Archives of Toxicology Springer-Verlag 85/4(2011-04-01), 355-361 0340-5761 85:4<355 2011 85 204 https://doi.org/10.1007/s00204-010-0586-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-010-0586-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Li Qing Department of Hygiene and Public Health, Nippon Medical School, 1-1-5 Sendagi, 113-8602, Bunkyo-ku, Tokyo, Japan aut NATIONALLICENCE 700 1- Kobayashi Maiko Department of Hygiene and Public Health, Nippon Medical School, 1-1-5 Sendagi, 113-8602, Bunkyo-ku, Tokyo, Japan aut NATIONALLICENCE 700 1- Kawada Tomoyuki Department of Hygiene and Public Health, Nippon Medical School, 1-1-5 Sendagi, 113-8602, Bunkyo-ku, Tokyo, Japan aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/4(2011-04-01), 355-361 0340-5761 85:4<355 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer