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[Studies on relationship between toxicity of trichothecene toxin T-2 and its structure]
1Institute of Toxicology and Pharmacology Academy of Military Medical Sciences, Beijing.
Abstract:
Toxic action of mycotoxin T-2 and its metabolite T-2 tetraol and deepoxy T-2; tetraol was studied by cytotoxicity and animal toxicity tests to explore the relationship between toxin T-2 and its structure. Restults showed that proliferation of LLC-PK1 cells and synthesis of DNA could be inhibited by both toxin T-2 and T-2 tetraol. Toxicity of toxin T-2 was 100 times greater than that of T-2 tetraol. There was no obvious toxicity to the proliferation of LLC-PK1 cells and synthesis of DNA in a dose of 10 mg/L deepoxy T-2 tetraol. But, toxin T-2 caused obvious damage in heart muscle and articular cartilage of chicken embryos, and T-2 tetraol and deepoxy T-2 tetraol in heart muscle, but not in articular cartilage. T-2 tetraol produced by hydrolysis of toxin T-2 had toxicity to certain extent, but its strength was significantly less than that of the latter. It suggests that the epoxide group in toxin T-2 played a determinant role for its toxicity. If epoxy cycle of the basic nucleus of the molecule is open, its toxicity will change significantly.
Insights
The epoxide group in T-2 toxin is crucial for its toxicity. While T-2 toxin and its metabolite T-2 tetraol inhibit cell proliferation and DNA synthesis, T-2 toxin is significantly more potent.
Area of Science:
- Toxicology
- Biochemistry
Context:
- Mycotoxins, such as T-2 toxin, pose significant health risks.
- Understanding the structure-toxicity relationship of mycotoxins is vital for risk assessment.
Purpose:
- To investigate the toxicological effects of T-2 toxin and its metabolites, T-2 tetraol and deepoxy T-2 tetraol.
- To elucidate the role of the epoxide group in T-2 toxin's toxic mechanism.
Summary:
- Cytotoxicity assays showed T-2 toxin and T-2 tetraol inhibit LLC-PK1 cell proliferation and DNA synthesis, with T-2 toxin being 100 times more potent.
- Deepoxy T-2 tetraol exhibited no significant toxicity at tested concentrations.
- Animal toxicity tests revealed T-2 toxin damages heart muscle and articular cartilage in chicken embryos, while T-2 tetraol and deepoxy T-2 tetraol primarily affected heart muscle.
Impact:
- The epoxide group in T-2 toxin is a key determinant of its toxicity.
- Opening the epoxy cycle significantly alters the mycotoxin's toxicological profile.
- Findings contribute to a better understanding of T-2 toxin's mechanism of action and potential health implications.