Institute of Anatomy, Medical Faculty, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany.
Toxicol Lett. 2011 Jan 15;200(1-2):8-18. doi: 10.1016/j.toxlet.2010.10.006. Epub 2010 Oct 19.
The Fusarium derived mycotoxin deoxynivalenol (DON) is frequently found in cereals used for human and animal nutrition. We studied effects of DON in non-transformed, non-carcinoma, polarized epithelial cells of porcine small intestinal origin (IPEC-1 and IPEC-J2) in a low (200 ng/mL) and a high (2000 ng/mL) concentration. Application of high DON concentrations showed significant toxic effects as indicated by a reduction in cell number, in cellular reduction capacity measured by MTT assay, reduced uptake of neutral red (NR) and a decrease in cell proliferation. High dose toxicity was accompanied by disintegration of tight junction protein ZO-1 and increase of cell cycle phase G2/M. Activation of caspase 3 was found as an early event in the high DON concentration with an initial maximum after 6-8 h. In contrast, application of 200 ng/mL DON exhibited a response pattern distinct from the high dose DON toxicity. The cell cycle, ZO-1 expression and distribution as well as caspase 3 activation were not changed. BrdU incorporation was significantly increased after 72 h incubation with 200 ng/mL DON and NR uptake was only transiently reduced after 24 h. Low dose effects of DON on intestinal epithelial cells were triggered by mechanisms different from those responsible for the high dose toxicity.
镰刀菌产生的真菌毒素脱氧雪腐镰刀菌烯醇（DON）经常出现在用于人类和动物营养的谷物中。我们研究了低浓度（200ng/ml）和高浓度（2000ng/ml）脱氧雪腐镰刀菌烯醇对猪小肠非转化、非癌、极化上皮细胞（IPEC-1 和 IPEC-J2）的影响。高浓度 DON 的应用表现出明显的毒性作用，表现为细胞数量减少、MTT 测定的细胞还原能力降低、中性红（NR）摄取减少和细胞增殖减少。高剂量毒性伴随着紧密连接蛋白 ZO-1 的解体和细胞周期 G2/M 期的增加。在高 DON 浓度下， caspase 3 的激活被发现是一个早期事件，在 6-8 小时后出现初始最大值。相比之下，应用 200ng/ml DON 表现出与高剂量 DON 毒性不同的反应模式。细胞周期、ZO-1 的表达和分布以及 caspase 3 的激活没有改变。在 200ng/ml DON 孵育 72 小时后，BrdU 掺入显著增加，NR 摄取在 24 小时后仅短暂减少。低剂量 DON 对肠道上皮细胞的作用是由与高剂量毒性不同的机制触发的。
