T-2 Toxin-Induced Apoptosis in Hematopoietic Tissues of Mice

Shinozuka, Junko; Suzuki, Masami; Noguchi, Noriko; Sugimoto, Testuro; Uetsuka, Koji; Nakayama, Hlroyuki; Doi, Kunio

doi:10.1177/019262339802600512

Cited by 74 publications

(41 citation statements)

References 23 publications

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“…Our reseach group first clarified that T-2 toxininduced death of lymphocytes in the thymus 6,7 , splenic white pulp 6,7 and Peyer's patches 8 is apoptosis. After that, our research group also confirmed that hematopoietic cells in the bone marrow and splenic red pulp 9 , and intestinal crypt epithelial cells 10 die through apoptosis following T-2 toxininoculation.…”

Section: Introductionsupporting

confidence: 54%

T-2 Toxin-Induced Apoptosis and c-fos mRNA Expression in Con A-Stimulated Mouse Thymocyte Primary Cultures.

et al. 2001

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Abstract:The development of apoptosis and the expression of c-fos mRNA were investigated up to 24 hours after treatment (HAT) with 0.2 g/ml of T-2 toxin in Con A-stimulated primary thymocyte cultures prepared from BALB/c mice. Cell viability began to decrease from 1 to 3 HAT, and it was approximately 50% at 6 HAT. The level of cytoplasmic nucleosomes peaked at 3 HAT (about 2 times of control) and decreased thereafter. At 6 HAT, thymocytes showed irregular-shaped or fragmented nuclei. By RT-PCR, the level of c-fos mRNA began to increase within 1 HAT, and maintained a high level through the observation period. Preincubation with BAPTA/AM, a intracellular calcium ion chelator, markedly suppressed the expression of c-fos mRNA and the level of DNA fragmentation induced by T-2 toxin. Although less effective, preincubation with H-7, a protein kinase C (PKC) inhibitor, also depressed the above-mentioned two parameters. These findings indicate that, in mouse thymocyte primary cultures treated with T-2 toxin, c-fos may play an important role in the induction of apoptosis and the increase in intracellular calcium ion may be closely related with the expression of c-fos mRNA. In addition, these findings also suggest that PKC-dependent pathway may be involved in T-2 toxin-induced thymocyte apoptosis. (J Toxicol Pathol 2001; 14: 247-251)

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Section: Introductionsupporting

confidence: 54%

T-2 Toxin-Induced Apoptosis and c-fos mRNA Expression in Con A-Stimulated Mouse Thymocyte Primary Cultures.

et al. 2001

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“…In the present study on rats, single cell necrosis was observed in the nervous system and liver of fetuses. Single cell necrosis of hematopoietic cells in the fetal liver was considered to be similar to that in the spleen and bone marrow in mice treated with T-2 toxin 26 . It has been considered that fetotoxicity of T-2 toxin is secondary to maternal toxicity 13 .…”

Section: Discussionmentioning

confidence: 99%

T-2 Toxin-Induced Morphological Changes in Pregnant Rats

et al. 2003

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Pregnant Wistar rats on day 13 of gestation were treated with T-2 toxin at a single oral dose of 2 mg/kg. Rats were sacrificed at 24 and 48 hours after treatment (HAT), and the dams, placenta and fetuses were subjected to histopathological examination. In the dams treated with T-2 toxin, single cell necrosis was observed in the thymus, spleen, liver, stomach, intestines, salivary glands and pancreas. In the liver, fatty change was also observed. In one dam at 24 HAT, hemorrhage from the vagina was observed macroscopically, and hemorrhage in the placenta and single cell necrosis of cytotrophoblasts were observed microscopically. In the fetuses, increase of single cell necrosis was observed in the central nervous system at 24 HAT. At 48 HAT, single cell necrosis of hematopoietic cells and hepatocytes was also increased in the liver. These results indicate that T-2 toxin may induce changes with similar histopathological nature in dam's organs, placentae and fetuses. These results also suggest that changes observed in the fetuses are caused by the direct effect of T-2 toxin. (J Toxicol Pathol 2003; 16: 59-65)

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“…4). On the other hand, mature granulocytes show no significant changes 27 . Such changes in the hematopoietic tissues result in a significant depression in the number of white blood cells in peripheral blood [27][28][29] .…”

Section: Hematopoietic Tissuesmentioning

confidence: 97%

“…On the other hand, mature granulocytes show no significant changes 27 . Such changes in the hematopoietic tissues result in a significant depression in the number of white blood cells in peripheral blood [27][28][29] . The spleen, which is composed of white and red pulp, is the largest lymphoid tissue in the circulation, and it is the site of erythrocyte storage and the removal of dysfunctional erythrocytes and leukocytes.…”

Section: Hematopoietic Tissuesmentioning

confidence: 97%

T-2 Toxin and Apoptosis

2006

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T-2 toxin is a cytotoxic fungal secondary metabolite produced by various species of Fusarium. This paper reviews the reported data about the development and/or mechanisms of T-2 toxin-induced apoptosis in the hematopoietic, lymphoid and gastrointestinal tissues, dorsal skin and fetal tissues of mice and rats. Apoptosis occurs earlier in hematopoietic tissues than in lymphoid tissues, and moreover there is a difference among lymphocyte populations in the susceptibility to T-2 toxin. C-fos plays an important role in the early phase of T-2 toxin-induced apoptosis in hematopoietic and lymphoid tissues through mobilization of [Ca 2+ ] i and the PKC-dependent pathway, but not through Fas/Fasligand or p53-related pathways. In the gastrointestinal tract, apoptosis develops earlier in the small intestine than in the stomach, and is more prominent in the small intestine than in the large intestine. In the dorsal skin topically treated with T-2 toxin, epidermal basal cell proliferating activity is first suppressed due to the elevated TGF-β 1 expression, and then basal cell apoptosis develops concomitantly with the elevation of c-fos, c-jun and TNF-α mRNAs expression. In the fetuses, T-2 toxin-induced apoptosis is mainly observed in the central nervous and skeletal systems. In the fetal brain, T-2 toxin induces oxidative stress, followed by activation of the MAPK-JNK-c-Jun pathway, finally resulting in apoptosis. The TNF receptor pathway may also be involved in T-2 toxin-induced apoptosis in the fetal brain. Thus, the development and mechanisms of T-2 toxin-induced apoptosis differ somewhat depending on the tissues affected. (J Toxicol Pathol 2006; 19: 15-27)

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T-2 Toxin-Induced Apoptosis in Hematopoietic Tissues of Mice

Cited by 74 publications

References 23 publications

T-2 Toxin-Induced Apoptosis and c-fos mRNA Expression in Con A-Stimulated Mouse Thymocyte Primary Cultures.

T-2 Toxin-Induced Apoptosis and c-fos mRNA Expression in Con A-Stimulated Mouse Thymocyte Primary Cultures.

T-2 Toxin-Induced Morphological Changes in Pregnant Rats

T-2 Toxin and Apoptosis

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