Effects of trichothecene mycotoxins on eukaryotic cells: a review.
The major products of the trichothecene mycotoxin biosynthetic pathway produced in a species- and sometimes isolate-specific manner by cereal-pathogenic Fusarium fungi include T-2 toxin, diacetoxyscirpenol, deoxynivalenol and nivalenol. This paper briefly reviews the major effects of such trichothecenes on the gross morphology, cytology and molecular signalling within eukaryotic cells. The gross toxic effects of select trichothecenes on animals include growth retardation, reduced ovarian function and reproductive disorders, immuno-compromization, feed refusal and vomiting. The phytotoxic effects of deoxynivalenol on plants can be summarized as growth retardation, inhibition of seedling and green plant regeneration. Trichothecenes are now recognized as having multiple inhibitory effects on eukaryote cells, including inhibition of protein, DNA and RNA synthesis, inhibition of mitochondrial function, effects on cell division and membrane effects. In animal cells, they induce apoptosis, a programmed cell death response. Current knowledge about the eukaryotic signal transduction cascades and downstream gene products activated by trichothecenes is limited, especially in plants. In mammalian cells, certain trichothecenes trigger a ribotoxic stress response and activate mitogen-activated protein kinases. DON mediates the inflammatory response by modulating the binding activities of specific transcription factors and subsequently inducing cytokine gene expression. Several genes are up-regulated in wheat in response to trichothecene mycotoxins; the significance, if any, of these genes in the host response to trichothecenes has yet to be elucidated.