Comparative cytotoxicity of deoxynivalenol, nivalenol, their acetylated derivatives and de-epoxy metabolites

Abstract

The cytotoxicity of the de-epoxy metabolites of trichothecenes nivalenol (NIV) and deoxynivalenol (DON) was determined and compared with the cytotoxicity of the respective toxin with an intact epoxy group and their acetylated derivatives. The cytotoxic effects was determined by using the 5-bromo-2'-deoxyuridine (BrdU) incorporation assay assessing DNA-synthesis. The toxicity of NIV and DON expressed as the concentration inhibiting 50% of the DNA synthesis (IC(50)), was occurring at similar micromolar concentrations (1.19+/-0.06 and 1.50+/-0.34 microM). The toxicity of fusarenon X (4-acetyl NIV) in the assay was similar to the toxicity of NIV, and the toxicity of 15-AcDON was equal to the toxicity of DON. 3-AcDON was less toxic than DON and 15-AcDON. The IC(50) value for de-epoxy DON was 54 times higher in the assay than the IC(50) for DON, while the IC(50) of de-epoxy NIV was 55 times higher than the IC(50) for NIV. The results verify previous findings that the de-epoxidation is a detoxification reaction.