Cytotoxic effects of nivalenol on HL60 cells

  • NAGASHIMA Hitoshi
    National Agriculture and Food Research Organization, National Food Research Institute
  • NAKAGAWA Hiroyuki
    National Agriculture and Food Research Organization, National Food Research Institute
  • IWASHITA Keiko
    National Agriculture and Food Research Organization, National Food Research Institute

Bibliographic Information

Other Title
  • HL60細胞に対するニバレノールの細胞毒性

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Abstract

To elucidate the underlying mechanism of nivalenol toxicity, we treated human promyelocytic leukemia HL60 cells with nivalenol for 24 h and investigated the toxin's effects on cell viability and interleukin (IL)-8 secretion. Whereas exposure to 1 μg/ml nivalenol led to slight morphologic damage, that after treatment with 3 or 10 μg/ml nivalenol was pronounced. In 5-bromo-2-deoxyuridine (BrdU) incorporation assays of the rate of cell proliferation, the mean 50% inhibitory concentration (IC50) of nivalenol was 0.16 μg/ml. The effect of nivalenol on mitochondrial succinic dehydrogenase activity was examined using the water-soluble tetrazolium-8 assay, in which the mean IC50 was 0.40 μg/ml. The activity of lactate dehydrogenase (LDH) released from the cytoplasm was very low, even at 10 μg/ml nivalenol, indicating that although treated cells had extensive morphologic damage, they did not burst. We used BrdU incorporation (the most sensitive indicator of cell viability) to assess the effect of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester (BAPTA-AM), which chelates intracellular calcium ion, on nivalenol toxicity. BrdU incorporation after concomitant treatment with nivalenol and BAPTA-AM was higher than that after treatment with nivalenol alone, indicating that the cytotoxicity of nivalenol is dependent in part on intracellular calcium ion. Further, the media of nivalenol-treated cells contained substantial amounts of IL-8, suggesting that this cytokine contributes to the nivalenol-caused pathologic phenomena.

Journal

  • JSM Mycotoxins

    JSM Mycotoxins 56 (2), 65-70, 2006

    Japanese Society of Mycotoxicology

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