The In Vitro Approach to the Cytotoxicity of a Trichothecene Mycotoxin Nivalenol

Japan Agricultural Research Quarterly
ISSN 00213551
NII recode ID (NCID) AA0068709X
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43-01-02.pdf338.23 KB

Trichothecene mycotoxins are toxic to leukocytes, and one of the leading symptoms of trichothecene toxicosis is leukopenia. In this study, therefore, to elucidate the underlying mechanism of toxicity, we treated promyelocyte (one of the leukocytes) -derived cell line HL60 with a trichothecene mycotoxin nivalenol for 24 h and investigated the toxin's effects. After treatment with 3 or 10 μg/mL nivalenol, morphologic damage was pronounced. The effect of nivalenol on cell proliferation (5-bromo-2-deoxyuridine (BrdU) incorporation) was examined, and the mean 50% inhibitory concentration was 0.16 μg/mL. At 3 and 10 μg/mL, internucleosomal DNA fragmentation, one of the hallmarks of apoptosis, was apparent. Concentrations of nivalenol-caused morphologic damage are in accordance with DNA fragmentation, indicating that nivalenol-caused morphologic change is due to apoptosis. The media of nivalenol-treated cells contained substantial amounts of interleukin (IL)-8, suggesting that IL-8 contributes to the nivalenol-induced phenomena. Conversely, nivalenol decreased monocyte chemotactic protein-1 secretion. We performed BrdU incorporation 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. BrdU incorporation after concomitant treatment with nivalenol and BAPTA-AM was higher than that after treatment with nivalenol alone. Likewise BAPTA-AM considerably attenuated nivalenol-induced IL-8 secretion. Taking both results together, it appears that nivalenol-caused cytotoxicity depends on intracellular calcium ion.

Date of issued

cell proliferation

HL60 cell


intracellular calcium ion

Publisher Japan International Research Center for Agricultural Sciences
Available Online
NII resource type vocabulary Journal Article
Volume 43
Issue 1
spage 7
epage 11
DOI 10.6090/jarq.43.7
Rights Japan International Research Center for Agricultural Sciences
Language eng

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