Chlorpyrifos induces apoptosis in human T cells.
It was found previously that organophosphorus pesticides (OPs) significantly inhibited cytotoxic T lymphocyte (CTL) activity. To explore the mechanism of OP-induced inhibition of CTL activity, the present study investigated whether OPs can induce cell death/apoptosis in T cells. Jurkat human T cells were treated with chlorpyrifos at 0-100 ppm for 2, 4, and 6h at 37 degrees C in vitro. It was found that chlorpyrifos induced cell death of Jurkat human T cells in a dose- and time-dependent manner, as shown by MTT and LDH assays. Then, it was investigated if chlorpyrifos-induced cell death consisted of apoptosis, as determined by analysis of Annexin-V staining and the intracellular level of active caspase-3 by flow cytometry, and DNA fragmentation analysis. It was found that chlorpyrifos induces apoptosis in Jurkat T cells in a dose- and time-dependent manner, as determined by analysis of Annexin-V staining. DNA fragmentation was detected when cells were treated with 50 or 100 ppm chlorpyrifos for 4 and 6h. Chlorpyrifos also induced an increase in intracellular active caspase-3 in Jurkat T cells in a dose- and time-dependent manner, and a caspase-3 inhibitor, Z-DEVD-FMK, significantly inhibited chlorpyrifos-induced apoptosis. These findings indicate that chlorpyrifos can induce apoptosis in human Jurkat T cell cells, and this effect is partially mediated by the activation of intracellular caspase-3.
Li
Qing
Q
Department of Hygiene and Public Health, Nippon Medical School, 1-1-5 Sendagi, 113-8602 Tokyo, Japan. qing-li@nms.ac.jp
Kobayashi
Maiko
M
Kawada
Tomoyuki
T
D017304:Annexin A5; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D004390:Chlorpyrifos / Q000633:toxicity*; D004247:DNA / Q000096:biosynthesis / Q000302:isolation & purification; D053938:DNA Fragmentation / Q000187:drug effects; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006801:Humans; D007202:Indicators and Reagents; D007306:Insecticides / Q000633:toxicity*; D019169:Jurkat Cells; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects*; D013778:Tetrazolium Salts; D013844:Thiazoles
D017304:Annexin A5; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D007306:Insecticides; D013778:Tetrazolium Salts; D013844:Thiazoles; D004247:DNA; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3; C022616:thiazolyl blue; D016650:Fluorescein-5-isothiocyanate; D004390:Chlorpyrifos