Apoptotic Effect of Combinations of T-2, HT-2, and Diacetoxyscirpenol on Human Jurkat T Cells

Abstract

Trichothecene type A mycotoxins, such as T-2, HT-2, and diacetoxyscirpenol (DAS), are known to induce cytotoxicity and apoptosis in different cell types. As all three Fusarium toxins may occur concomitantly in a given food or feed commodity, there is growing interest in the effect of such mycotoxin mixtures. This study aimed to identify the toxic interactions among T-2, HT-2, and DAS in a human Jurkat cell model. As a first step, an MTT assay was used to assess cytotoxicity after 24 h of cell exposure to individual mycotoxins and their mixtures. The results were used to calculate the combination index (CI), which indicates the nature of the mycotoxin interactions. In Jurkat T cells, the toxicity ranking for the individual mycotoxins was T-2 > HT-2 > DAS. The CI values of the dual and triple mycotoxin combinations calculated from the results of the MTT and reactive oxygen species assays showed synergistic effects at low concentrations and an apparent antagonism at very high concentrations for all combinations. The additional cytometric analyses confirmed the synergistic effects, as expected, following co-exposure to the three tested trichothecenes. As the lower toxin concentrations investigated reflect natural contamination levels in food and feeds, the synergistic effects identified should be considered in risk characterization for trichothecene exposure in humans and animals.