We examined T-2 toxin-induced lesions in the bone marrow and splenic red pulp as many as 48 hr after oral inoculation with 10 mg/kg body weight of T-2 toxin in female ICR:CD-1 mice. Histopathologically, the bone marrow and splenic red pulp showed a significant hypocellularity. In the bone marrow, the number of myelocytes significantly decreased due to the loss of immature granulocytes, erythroblasts, and lymphocytes. The nuclei of the remaining cells showing pyknosis or karyorrhexis were positively stained by the TdT-mediated dUTP nick end labeling (TUNEL) method, and these TUNEL-positive cells showed ultrastructural characteristics of apoptosis. With agarose gel electrophoresis, DNA ladders were clearly detected in bone marrow samples. The number of TUNEL-positive cells in splenic red pulp increased earlier than it did in the splenic white pulp. Thus, T-2 toxin induced-lesions in the hematopoietic tissues and in the lymphoid tissues were brought about by apoptosis of component cells. We believe that damage to the hematopoietic microenvironment may also play an indirect role in the induction of apoptosis in the bone marrow.
1. Bilgrami KS, Masood A, and Rahman MF (1995). Cumulative effect of T-2 toxin and vitamin C on chromosomal abnormalities in the bone marrow cells of mice (Sins musculus). Cytobios. 81: 171–174.
2.
2. Deloach JR, Gyongyossy-Issa MIC, and Khachatouriants GG (1989). Species-specific hemolysis of erythrocytes by T-2 toxin. Toxicol. Appl. Pharmacol.. 97: 107–112.
3.
3. Friend SC, Hancock DS, Schiefer HB, and Babiuk LA (1983). Experimental T-2 toxicosis in sheep. Can. J. Com. Med.. 47: 291–297.
4.
4. Gavrieli Y, Sherman Y, and Ben-sasson SA (1992). Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J. Cell Biol.. 119: 493–501.
5.
5. Glavits R, Vanyi A, Fekete S, and Tamas J (1989). Acute toxico-logical experiment of T-2 toxin in rabbits. Acta Vet. Hung.. 37: 75–79.
6.
6. Gyongyossy-Issa MIC and Khachatourians GG (1984). Interaction of T-2 toxin with murine lymphocytes. Biochim. Biophys. Acta. 803: 197–202.
7.
7. Hayes MA, Bellamy JE, and Schiefer HB (1980). Subacute toxicity of dietary T-2 toxin in mice: Morphological and hematological effects. Can. J. Com. Med.. 44: 203–218.
8.
8. Holladay SD, Smith BJ, and Luster MI (1995). B lymphocyte precursor cells represent sensitive targets of T2 mycotoxin exposure. Toxicol. Appl. Pharmacol.. 131: 309–315.
9.
9. IARC (1993). Some naturally occurring substances: Food items and constituents, heterocyclic aromatic amines and mycotoxin. In: IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans.Lyon, France, pp. 467–488.
10.
10. Joffie A (1978). Fusarium poaeand F. sporolrichioidesas principal causal agents of alimentary toxic aleukia, Vol. 3. In: Mycotoxic Fungi, Mycotoxins and Mycotoxicoses, T Wylie and L Morehouses (eds). Marcel Dekker, New York, pp. 21–59.
11.
11. Li G, Shinozuka J, Uetsuka K, Nakayama H, and Doi K (1997). T-2 toxin-induced apoptosis in intestinal crypt epithelial cells in mice. Exp. Toxicol. Pathol.. 49: 447–450.
12.
12. Li G, Shinozuka J, Uetsuka K, Nakayama H, and Doi K (1997). T-2 toxin-induced apoptosis in Peyer's patches of mice. J. Toxicol. Pathol.. 10: 59–61.
13.
13. Lutsky I and Mor N (1981). Experimental alimentary toxic aleukia in cats. Lab. Anim. Sci.. 31: 43–47.
14.
14. Matumoto K, Inukai S, Isaka T, Aruga N, Nakamura S, Nagasawa T, and Naito J (1995). Cell counts in peripheral blood and bone marrow of male C.B-17 scid/scid mice. Lab. Anim.. 29: 218–222.
15.
15. Mirocha CJ and Pathre S (1973). Identification of the toxic principle in a sample of poaefusarin. Appl. Microbiol.. 26: 719–724.
16.
16. Norppa H, Penttila M, Sorsa M, Hintikka EL, and Ilus T (1980). Mycotoxin T-2 of Fusarium tricinctumand chromosome changes in Chinese hamster bone marrow. Hereditas. 93: 329–332.
17.
17. Pang VF, Lorenzana RM, Beasley VR, Buck WB, and Haschek WM (1987). Experimental T-2 toxicosis in swine. III. Morphologic changes following intravascular administration of T-2 toxin. Fun-dam. Appl. Toxicol.. 8: 298–309.
18.
18. Preziosi R, Sarli G, Benazzi C, and Marcato PS (1995). Detection of proliferating cell nuclear antigen (PCNA) in canine and feline mammary tumours. J. Comp. Pathol.. 113: 301–313.
19.
19. Quiroga MA, Itagaki S, and Doi K (1993). Early ultrastructural changes of thymocytes in T-2 toxicated mice. J. Toxicol. Pathol.. 6: 109–112.
20.
20. Rosenstein Y and Lafarge FC (1983). Inhibitory effect of FusariumT2-toxin on lymphoid DNA and protein synthesis. Toxicol. Appl. Pharmacol.. 70: 283–288.
21.
21. Sato N, Ueno Y, and Enomoto M (1975). Toxicological approaches to the toxic metabolites of Fusaria. VIII. Acute and subacute toxicities of T-2 toxin in cats. Jpn. J. Pharmacol.. 25: 263–270.
22.
22. Segal R, Milo-Goldzweig I, Joffe AZ, and Yagen B (1983). Tri-chothecene-induced hemolysis. I. The hemolytic activity of T-2 toxin. Toxicol. Appl. Pharmacol.. 70: 343–349.
23.
23. Seifert MF and Marks SC (1985). The regulation of hemopoiesis in the spleen. Experimentia. 41: 192–199.
24.
24. Sharma RP (1993). Immunotoxicity of mycotoxins. J. Dairy Sci.. 76: 892–897.
25.
25. Shinozuka J, Guanmin L, Kiatipattanasakul W, Uetsuka K, Nakayama H, and Doi K (1997). T-2 toxin-induced apoptosis in lymphoid organs of mice. Exp. Toxicol. Pathol.. 49: 387–392.
26.
26. Shinozuka J, Guanmin L, Uetsuka K, Nakayama H, and Doi K (1997). Process of the development of T-2 toxin-induced apoptosis in lymphoid organs of mice. Exp. Anim.. 46: 117–126.
27.
27. Smith BJ, Holladay SD, and Blaylock BL (1994). Hematopoietic alterations after exposure to T-2 mycotoxin. Toxicon. 32: 1115–1123.
28.
28. Stanford GK, Hood RD, and Hayes AW (1975). Effect of prenatal administration of T-2 toxin to mice. Res. Commun. Chem. Pathol. Pharmacol.. 10: 743–746.
29.
29. Ueno Y, Nakajima M, Sakai K, Ishi K, Sato N, and Shimada N (1973). Comparative toxicology of Trichothec mycotoxins: Inhibition of protein synthesis in animal cells. J. Biochem.. 74: 285–296.
30.
30. Velazco V, Faifer GC, and Godoy HM (1996). Differential effects of T-2 toxin on bone marrow and spleen erythropoiesis in mice. Food Chem. Toxicol.. 34: 371–375.
31.
31. Williams PP (1989). Effects of T-2 mycotoxin on gastrointestinal tissues: A review of in vivo and in vitro models. Arch. Environ. Contain. Toxicol.18: 374–387.
