Toxicity of epoxy trichothecenes in cultured mammalian cells

Abstract

With four established cell lines, cytotoxicity of 23 epoxy trichothecenes was tested. Three cell lines from human origin have been found to have a similar degree of sensitivity to trichothecenes. A pig kidney cell line had a higher sensitivity to NT-1 toxin, neosolaniol, tetraacetyl T-2, and iso-T-2 toxin. The potential cause for discrepancies in literature were discussed. Activity of esterases in calf serum used for cell cultures should be recorded whenever conducting toxicity tests in cell cultures with trichothecenes.Relations of chemical structures of toxins to their biological activities were investigated. With verrucarol (scirpendiol), scirpentriol, and T-2 tetraol analogues the esters generally showed significantly higher cytotoxicity. But, loss of acetyl groups at single positions did not necessarily mean decline in toxicity. With macrocyclic trichothecenes minor differences in the side chain of verrucarol esters were found to contribute to differences in biological activity.