Trichothecenes cytotoxicity

The ability of the trichothecenes to produce dermal toxicity is rather unusual for toxins. While only the more potent trichothecene mycotoxins have this effect, the cytotoxicity produced on contact with feed may result in lesions on the snout, muzzle, lips, and tongue of animals. Similar dermal effects have been reported in humans and in swine following topical application of T-2 toxin. T-2 toxin, DAS,... 

The trichothecene mycotoxins are cytotoxic to most eukaryotic cells.46 A number of cytotoxicity assays have been developed and include survival and cloning assays, measuring protein and deoxyribonucleic acid (DNA) synthesis by radiolabeling procedures, and a neutral red cell-viability assay. A minimum of 24 to 48 hours is required to measure the effects of the trichothecene mycotoxins on cell viability. 

Toxin-stimulated alteration in mitochondrial membranes contributes to the effects on cellular energetics and cellular cytotoxicity. Although initial investigations on the mechanism of action of the trichothecene mycotoxins suggested that the inhibition of protein synthesis as the principal mechanism of action, the above observations indicate that the effects of these toxins are much more diverse. 

C24H34O, Mr 466.53, mp. 151 - I52°C, needles, [a] -15.5° (CHClj), a mycotoxin of the tric(h)othecene type formed by Gibberella zeae. various Fusarium species, and Trichoderma lignorum. T. exhibits the typical properties of a trichothecene compound, such as emetic, skin irritating, cytotoxic activities and skin necrosis. LD50 (mouse i. p.) 3 mg/kg. The previously suggested cancerogenic activity was not confirmed. As a... 

Cytotoxicity tests, using a range of tissue cultures, would seem to provide a system more closely related to the whole animal. Baby hamster kidney cells, and human cells lines such as HEp-11, which are especially sensitive to trichothecenes, and Chang liver cells, have been successfully used for screening for the presence of toxic metabolites in food extracts. 

Trichothecenes are directly cytotoxic to a variety of cells in vitro. The mechanism is unclear, but direct cytotoxicity may explain the dermonecralic effects repotted for trichothecenes. 

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