Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100, Burjassot, Valencia, Spain.
Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100, Burjassot, Valencia, Spain.
Food Chem Toxicol. 2020 Nov;145:111654. doi: 10.1016/j.fct.2020.111654. Epub 2020 Aug 7.
The T-2 toxin (T-2) is a type A trichothecene produced by Fusarium species, and the most cytotoxic mycotoxin of the group. A study was made to determine T-2 cytotoxicity in human hepatocarcinoma (HepG2) cells; evaluate whether there is an adaptive response of HepG2 cells exposed to low concentrations of T-2; identify the T-2 metabolites by LC-Q-TOF MS; and determine whether T-2 disrupts cell proliferation in HepG2 cells. The IC values obtained ranged from 61.9 ± 2.4 nM to 70.7 ± 7.4 nM. No adaptive response was observed. There was no evidence of extra- or intracellular accumulation of T-2 after 24 h of exposure as determined by LC-Q-TOF MS. However, some T-2 metabolites such as HT-2 toxin, neosolaniol and T-2 triol showed important (>75%) intracellular accumulation. Cell distribution was significantly increased in SubG0/G1 phase (11.8-fold higher) and decreased (12%) in G2/M phase at 60 nM T-2, versus the control. Simultaneously, increased necrosis (238%) and apoptosis/necrosis (up to 35.5%) were observed in HepG2 cells exposed to T-2. In conclusion, the results show that T-2 leads to loss of cell viability without an adaptive response, and that the metabolites generated play an important role in T-2 cytotoxicity, increasing HepG2 cell damage.
T-2 毒素（T-2）是一种由镰刀菌属产生的 A 型单端孢霉烯族化合物，也是该族中最具细胞毒性的真菌毒素。本研究旨在确定 T-2 在人肝癌（HepG2）细胞中的细胞毒性；评估 HepG2 细胞暴露于低浓度 T-2 时是否存在适应性反应；通过 LC-Q-TOF MS 鉴定 T-2 的代谢物；并确定 T-2 是否会破坏 HepG2 细胞的增殖。获得的 IC 值范围为 61.9±2.4 nM 至 70.7±7.4 nM。未观察到适应性反应。通过 LC-Q-TOF MS 确定，暴露 24 小时后，没有证据表明 T-2 在外或细胞内积累。然而，一些 T-2 代谢物，如 HT-2 毒素、新茄病镰刀菌醇和 T-2 三醇，显示出重要的（>75%）细胞内积累。与对照组相比，在 60 nM T-2 作用下，细胞分布在 SubG0/G1 期（高 11.8 倍）显著增加，而在 G2/M 期减少（减少 12%）。同时，暴露于 T-2 的 HepG2 细胞中观察到坏死（增加 238%）和凋亡/坏死（高达 35.5%）增加。总之，结果表明 T-2 导致细胞活力丧失而无适应性反应，并且生成的代谢物在 T-2 细胞毒性中起重要作用，增加 HepG2 细胞损伤。
