Apoptotic cellular damage in mice after T-2 toxin-induced acute toxicosis.
By histopathologic, electron microscopic, and immunochemical observation, the mechanism of cellular death was investigated in thymus, spleen, and liver of mice given intraperitoneally sublethal doses of T-2 toxin, a trichothecene mycotoxin. In the thymus and spleen of mice given 5.0 mg/kg body weight of T-2 toxin and killed 12 hours later, a massive cellular destruction characterized by chromatin condensation was evident, and electron microscopy analysis revealed the presence of apoptotic bodies. In the liver of mice given 2.5 mg/kg of T-2 toxin and killed 2 hours later, the induction of apoptotic cellular lesions was observed by electron microscopy, and Kupffer cells phagocytosed the apoptotic bodies. Such lesions were not observed in the mice killed 12 hours after receiving the toxin. In situ nick translation analysis (Tunel method) revealed DNA fragmentation in thymus, spleen, and liver shortly after administration of T-2 toxin. As previously observed in vitro, these findings indicated that T-2 toxin is a potent inducer of apoptotic cell death in thymus, spleen, and liver in vivo; especially in liver, apoptosis is induced rapidly as compared with the other tissues observed, and Kupffer cells play an important role for clearance of apoptosis.
Ihara
T
T
Department of Pathology, Institute of Tochigi Clinical Pathology, Tochigi, Japan.
Sugamata
M
M
Sekijima
M
M
Okumura
H
H
Yoshino
N
N
Ueno
Y
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D005260:Female; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D013154:Spleen / Q000187:drug effects* / Q000473:pathology; D013605:T-2 Toxin / Q000633:toxicity*; D013950:Thymus Gland / Q000187:drug effects* / Q000473:pathology
D013605:T-2 Toxin