Biohazard Prevention Centre, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
Military Institute of Armament Technology, Prymasa Stefana Wyszyńskiego 7, 05-220 Zielonka, Poland.
Int J Mol Sci. 2023 Sep 22;24(19):14458. doi: 10.3390/ijms241914458.
T-2 mycotoxin is the most potent representative of the trichothecene group A and is produced by various species, including , , and . T-2 toxin has been reported to have toxic effects on various tissues and organs, and humans and animals alike suffer a variety of pathological conditions after consumption of mycotoxin-contaminated food. The T-2 toxin's unique feature is dermal toxicity, characterized by skin inflammation. In this in vitro study, we investigated the molecular mechanism of T-2 toxin-induced genotoxicity in the human skin fibroblast-Hs68 cell line. For the purpose of investigation, the cells were treated with T-2 toxin in 0.1, 1, and 10 μM concentrations and incubated for 24 h and 48 h. Nuclear DNA (nDNA) is found within the nucleus of eukaryotic cells and has a double-helix structure. nDNA encodes the primary structure of proteins, consisting of the basic amino acid sequence. The alkaline comet assay results showed that T-2 toxin induces DNA alkali-labile sites. The DNA strand breaks in cells, and the DNA damage level is correlated with the increasing concentration and time of exposure to T-2 toxin. The evaluation of nDNA damage revealed that exposure to toxin resulted in an increasing lesion frequency in Hs68 cells with and genes. Further analyses were focused on mRNA expression changes in two groups of genes involved in the inflammatory and repair processes. The level of mRNA increased for all examined inflammatory genes (, , , and ). In the second group of genes related to the repair process, changes in expression induced by toxin in genes- and were observed. The level of mRNA for decreased, while that for increased. In the case of , , and , no changes in mRNA level between the control and T-2 toxin probes were observed. In conclusion, the results of this study indicate that T-2 toxin shows genotoxic effects on Hs68 cells, and the molecular mechanism of this toxic effect is related to nDNA damage.
T-2 真菌毒素是 A 类单端孢霉烯族化合物中最具毒性的代表，由多种物种产生，包括 、 和 。据报道，T-2 毒素对各种组织和器官具有毒性作用，人类和动物在食用受真菌毒素污染的食物后会出现多种病理状况。T-2 毒素的独特特征是皮肤毒性，表现为皮肤炎症。在这项体外研究中，我们研究了 T-2 毒素在人皮肤成纤维细胞-Hs68 细胞系中诱导遗传毒性的分子机制。为此，我们用 0.1、1 和 10 μM 浓度的 T-2 毒素处理细胞，孵育 24 小时和 48 小时。真核细胞的核 DNA（nDNA）位于细胞核内，具有双螺旋结构。nDNA 编码蛋白质的一级结构，由基本氨基酸序列组成。碱性彗星试验结果表明，T-2 毒素诱导 DNA 碱不稳定位点。细胞中的 DNA 链断裂，DNA 损伤水平与 T-2 毒素暴露浓度和时间的增加呈正相关。nDNA 损伤的评估表明，暴露于毒素会导致 Hs68 细胞中 和 基因的损伤频率增加。进一步的分析集中在与炎症和修复过程相关的两组基因的 mRNA 表达变化上。所有检测到的炎症基因（ 、 、 和 ）的表达水平都增加了。在与修复过程相关的第二组基因中，观察到毒素在 和 基因中诱导的表达变化。mRNA 水平 降低，而 增加。对于 、 和 基因，在对照和 T-2 毒素探针之间未观察到 mRNA 水平的变化。总之，本研究结果表明 T-2 毒素对 Hs68 细胞具有遗传毒性作用，这种毒性作用的分子机制与 nDNA 损伤有关。
