Toxicity of the mycotoxins fumonisins B1 and B2 and Alternaria alternata f. sp. lycopersici toxin (AAL) in cultured mammalian cells |
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Authors: | W. T. Shier H. K. Abbas C. J. Mirocha |
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Affiliation: | (1) Department of Medicinal Chemistry, University of Minnesota, 55108 St. Paul, MN, USA;(2) Department of Plant Pathology, University of Minnesota, 55108 St. Paul, MN, USA;(3) Present address: Southern Weed Science Laboratory, ARS, USDA, 38776 Stoneville, MS, USA |
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Abstract: | Fumonisins B1 and B2 and AAL toxin are a series of structurally related mycotoxins. Fumonisins B1 and B2, produced by Fusarium moniliforme Sheldon induce toxic hepatitis and hepatomas in rats and leukoencephalomalacia in horses. The cancer-promotion assay which has been used to guide their purification is slow and consumes large amounts of sample. We have examined a series of cultured mammalian cell lines in order to develop a more rapid and sensitive bioassay system, which may be useful for examining structure-activity relationships and the mechanism(s) of action of these toxins. Of 9 rat hepatoma cell lines tested, all except the two most de-differentiated lines were sensitive to the three toxins, with a toxic response visible by 48 h. Approximate IC50 values for the most sensitive hepatoma line, H4TG, were 4, 2 and 10 g/ml for fumonisins B1, B2 and AAL toxin, respectively in 100 l cultures. Among 15 cell lines from other sources, only MDCK dog kidney epithelial cells were sensitive (IC50 = 2.5, 2 and 5 g/ml, respectively). Studies in co-cultures of sensitive and insensitive cell lines and in cultures of a sensitive cell line over a range of cell densities indicated that cytotoxicity of fumonisins B1 and B2 does not involve metabolite activation to a derivative stable enough to diffuse to adjacent cells.Abbreviations AAL toxin Alternaria alternata f. sp. lycopersici toxin - IC50 concentration giving 50% inhibition of cell proliferation |
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Keywords: | Fumonisin B1 fumonisin B2 AAL toxin T-2 toxin mycotoxin Fusarium moniliforme bioassay cell culture |
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