Development of Apoptosis and Changes in Apoptosis-related Genes Expression in the Mouse Thymus Following T-2 Toxin-inoculation.

  • Shinozuka Junko
    Department of Veterinary Pathology, Faculty of Agriculture, The University of Tokyo
  • Tsutsui Shigeki
    Department of Biomedical Science, Faculty of Agriculture, The University of Tokyo
  • Ishigami Noriaki
    Department of Veterinary Pathology, Faculty of Agriculture, The University of Tokyo
  • Ueno-Yamanouchi Aito
    Department of Veterinary Pathology, Faculty of Agriculture, The University of Tokyo
  • Nakayama Hiroyuki
    Department of Veterinary Pathology, Faculty of Agriculture, The University of Tokyo
  • Doi Kunio
    Department of Veterinary Pathology, Faculty of Agriculture, The University of Tokyo

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T-2 toxin is a kind of trichothecene mycotoxin produced by species of the genus Fusarium, and it attacks the tissues containing a large number of actively dividing cells such as lymphoid and hematopoietic tissues. The development of apoptosis and the changes in mRNA expressions of apoptosis-related cell-surface antigen (Fas) and genes (p53, bcl-2, c-myc, and c-fos) were investigated in the thymus up to 9 hours after oral inoculation (HAI) with 10 mg/kg body weight of T-2 toxin in female ICR: CD-1 mice. The number of TUNEL-positive lymphocytes clearly increased in the thymus of T-2 toxin-inoculated mice at 6 and 9 HAI. By agarose gel electrophoresis, DNA ladder was clearly detected at 9 HAI. The c-fos mRNA expression increased prior to the progression of apoptotic cell death in the thymus of T-2 toxin-inoculated mice. As to Fas, p53, bcl-2, and c-myc, their mRNA expressions showed no significant changes through the observation period. The results using p53 knockout mice and Fas disfunctional mutant mice also demonstrated that p53 and Fas had no relation to T-2 toxin-induced apoptosis. These findings suggest that c-fos mRNA induction may be associated with T-2 toxin-induced lymphocyte apoptosis.

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