Trichothecene-induced cytotoxicity on human cell lines

Abstract

Trichothecene cytotoxicity of type A (T-2 toxin and HT-2 toxin), type B (deoxynivalenol, DON, and nivalenol, NIV), and type D (satratoxins G and H) compounds was determined comparatively by using eight permanent human cell lines (Hep-G2, A549, CaCo-2, HEp-2, A204, U937, RPMI 8226, and Jurkat). Viability of cells was measured by a water-soluble tetrazolium (WST-1) reagent cell proliferation assay assessing mitochondrial metabolic activity. Toxicity was expressed as the toxin concentration inhibiting 50% of cell viability (IC50). Depending on the chemotype of the tested trichothecenes, relative cytotoxic activity differed by a factor of 100-1,000, and the corresponding IC50 values were in the range from 2.2 nmol/l (satratoxin H on Jurkat and U937 cells) to 4,900 nmol/l (deoxynivalenol on HEp-2 cells). In contrast, the specific toxicity of each individual mycotoxin towards different cell lines was within remarkable close limits, and between-cell line differences were much smaller than previously reported. For the cell lines tested, IC50 values were 4.4-10.8 nmol/l for T-2 toxin, 7.5-55.8 mol/l for HT-2 toxin, 600-4,900 nmol/l for DON, 300-2,600 nmol/l for NIV, and 2.2-18.3 nmol/l for satratoxins G/H. In addition, for the first time, the toxic activity of trichothecenes on primary cell culture of human endothelial cells (HUVEC) was tested. The susceptibility of this cell line was comparable to the other cell lines tested, with IC50 values ranging from 16.5 nmol/l (T-2 toxin) to 4,500 nmol/l (DON). The results suggest that the current focus of cytotoxicological studies on trichothecenes on lymphoid cell lines may lead to an underestimate of their potential on other target cell systems.

Assessment of toxic potential of mycotoxin contaminated bread during in vitro human digestion on human B lymphoid cell line

“…Immunotoxicity of both mycotoxins demonstrated in this study was in agreement with data obtained by Nielsen et al (2009) by assaying the same B human lymphoid cell line. On other human lymphoid cell lines different IC 50 values were calculated, and values obtained for HT-2 were 10 times lower than those calculated for T-2 (Visconti et al, 1991).…”

Induction of MAPK-dependent transcription factors by deoxynivalenol in human cell lines

“…Furthermore, influence on several basic metabolic parameters in human primary hepatocytes was shown (Königs et al 2008). In addition, a comprehensive study indicated comparable high levels of DON toxicity between nine different human cell lines (Nielsen et al 2009b). These data suggest that the current research focus on lymphoid cell lines may lead to an underestimate of the toxic potential of DON.…”

“…Nielsen et al 2009b), respond differently compared to the more resistant Hep-G2 and A204 cells. Distinct increases in FOS levels, induced by treatment of cells with 1 µmol/l DON for 3 h, were observed in Hep-G2 and U937 cells…”

Biotoxin Detection Using Cell-Based Sensors

“…can be found in a comprehensive review published earlier [74]. It is also important to note that application of multiple cell lines of different origins to test same mycotoxins reveals more accurate estimations of toxicity particularly for toxins with moderate to low cytotoxic potency [74,75]. Recently a study reported the generation of reactive oxygen species (ROS) and mammalian heat shock protein (Hsp) 70 expression in green monkey kidney (Vero) cells upon concurrent exposures to Fusarium mycotoxins, ZEN and T-2 toxin as a detection strategy to evaluate toxicity of these mycotoxins [23].…”