Comparative Toxicology of Trichothec Mycotoxins: Inhibition of Protein Synthesis in Animal Cells<xref ref-type="fn" rid="fn1"><sup>*</sup></xref>

Abstract

The inhibitory effects of fourteen kinds of 12-13-epoxy trichothec mycotoxins and related antibiotics on protein and DNA syntheses in reticulocytes, Ehrlich ascites tumor cells, rat liver and bacteria were investigated in whole-cell and cell-free systems, and the following results were obtained; 1. Among the fourteen compounds tested, twelve trichothecenes inhibited the uptake of 14C-leucine by whole cells of rabbit reticulocytes. The inhibitory effect varied over a wide range on chemical modification of the side chain and double bond. 2. In Ehrlich ascites tumor cells, the mycotoxins inhibited the uptake of 14C-leucine and 14C-thymidine without affecting that of14C-uracil. 3. When rabbit reticulocytes were treated with low concentrations of the trichothecenes, a marked degradation of polyribosomes was observed. 4. In cell-free systems of reticulocytes and rat liver, the trichothecenes inhibited the poly-U-dependent synthesis of polyphenylalanine in concentrations lower than the inhibitory concentrations of puromycin and cycloheximide, and the concentrations of various trichothecenes required for 50% inhibition were correlated with their lethal doses in mice. 5. In whole-cell and cell-free systems of Escherichia coli, fusarenon-X did not inhibit protein synthesis. A high concentration of the mycotoxin, slightly inhibited the uptake of 14C-amino acid in yeast (Geolrichum candidum). 6. Biochemical features of the actions of the trichothec mycotoxins were discussed in relation to their chemical and toxicological characteristics.