T-2 toxin induces thymic apoptosis in vivo in mice.

Abstract

A single intraperitoneal injection of T-2 toxin (0.35, 1.75, or 3.5 mg/kg body wt) induced time- and dose-dependent thymic atrophy in young female BALB/c mice. T-2 toxin (1.75 mg/kg) induced maximal atrophy by day 3 with complete recovery by day 7. Flow cytometric analysis showed that the CD4(+)CD8(+) double positive thymocyte population decreased markedly. Histopathological examination of the thymus indicated that the pattern of cell death in the thymocytes had a characteristic apoptotic morphology with cell shrinkage and nuclear condensation. The in vivo effects of T-2 toxin included the induction of DNA fragmentation of approximately 200 base pairs in ladder form and cell death in thymocytes. Furthermore, flow cytometric analysis of PI-stained thymocytes from animals dosed with T-2 toxin revealed the formation of apoptotic cells. Of nine kinds of trichothecene mycotoxins tested, T-2 toxin appeared to be the most potent agent to induce apoptosis in the thymus. We sought insight into the mechanism of T-2 toxin-induced apoptosis in vivo. Administration of the protein synthesis inhibitor, CHX (15 mg/kg ip), 5 min after T-2 toxin (1.75 mg/kg ip) inhibited the induction of apoptosis in thymocytes, suggesting that the de novo protein synthesis was necessary. By using adrenalectomized mice and anti-TNF-alpha antibody-injected mice, it was shown that neither endogenous glucocorticoid nor TNF-alpha appeared to be involved in the apoptotic process. Taken together, these findings suggest that T-2 toxin-induced thymic atrophy is associated with cell death through a mechanism of apoptosis.

• Authors: Z Islam, M Nagase, T Yoshizawa, K Yamauchi, N Sakato
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 148 Issue 2 Pg. 205-14 (Feb 1998) ISSN: 0041-008X [Print] United States
• PMID: 9473527 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright 1998 Academic Press.

Chemical References

• Antibodies
• Glucocorticoids
• Mycotoxins
• Protein Synthesis Inhibitors
• Tumor Necrosis Factor-alpha
• Cycloheximide
• T-2 Toxin

Topics

• Animals
• Antibodies (immunology)
• Apoptosis (drug effects)
• Atrophy
• CD4-CD8 Ratio (drug effects)
• Cycloheximide (pharmacology)
• DNA Fragmentation (drug effects)
• Female
• Flow Cytometry
• Glucocorticoids (metabolism)
• Mice
• Mice, Inbred BALB C
• Microscopy, Electron
• Mycotoxins (toxicity)
• Protein Synthesis Inhibitors (pharmacology)
• T-2 Toxin (antagonists & inhibitors, toxicity)
• T-Lymphocyte Subsets (immunology)
• Thymus Gland (drug effects, pathology, ultrastructure)
• Tumor Necrosis Factor-alpha (immunology, metabolism)