T-2 toxin and its metabolites: Characterization, cytotoxic mechanisms and adaptive cellular response in human hepatocarcinoma (HepG2) cells.

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.