Differential Association of T-2 and T-2 Tetraol with Mammalian Cells
ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
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The interactions of T-2 and its metabolite T-2 tetraol hereafter tetraol with CHO Chinese hamster ovary cells and ribosomes were studied. Trichothescenes are a group of structurally related sesquiterpenoids produced by several species of fungi. Trichothecenes are demonstrably lethal to many animal species and have been implicated as the causative agents in human disease and death. Although the pathogenesis of toxicity in animals is complex and not well defined, it is clear that trichothecenes are potent inhibitors of eukaryotic protein synthesis. Work from a number of laboratories has shown that trichothecenes block protein synthesis by binding to the 60S subunit of the eukaryotic ribosome. Although these toxins apparently bind to a common site mechanistically, some appear to inhibit initiation, whereas others block elongation or termination. Generally, the initiation-inhibiting toxins are more potent than the elongationtermination inhibitors. The basis for these potency differences is not clear and could be due to differences in such events as entry into the cell, binding to ribosomes, metabolism, etc. Data suggest that entry into target cells may be a major factor determining potency toxicity of trichothecene toxins for cells. Reprints.
- Genetic Engineering and Molecular Biology