Toxicity of the mycotoxins fumonisins B₁ and B₂ and Alternaria alternata f. sp. lycopersici toxin (AAL) in cultured mammalian cells

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 μg/ml for fumonisins B₁, B₂ and AAL toxin, respectively „in 100 μl cultures. Among 15 cell lines from other sources, only MDCK dog kidney epithelial cells were sensitive (IC₅₀ = 2.5, 2 and 5 μg/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.