Less-toxic rearrangement products of NX-toxins are formed during storage and food processing

Toxicol Lett. 2018 Mar 1:284:205-212. doi: 10.1016/j.toxlet.2017.12.016. Epub 2017 Dec 23.

Abstract

A new type A trichothecene mycotoxin, NX-2, was previously reported to be produced by North American isolates of the cereal pathogen Fusarium graminearum. Here we describe the isolation and structural characterization of a rearrangement product, called NX2-M1, and related compounds with different acetylation patterns (NX3-M1 and NX4-M1). In the NX-M1 derivatives, the epoxide ring is opened, and a covalent bridge between C-10 and C-12 of the trichothecene backbone is formed. In vitro translation assays showed that NX3-M1 is less toxic for eukaryotic ribosomes than NX-3. NX3-M1 also has a greatly reduced cytotoxic potential on two tested human colon cell lines. Formation of NX3-M1 can therefore be regarded as a detoxification reaction. The related F. graminearum mycotoxin deoxynivalenol (DON), which is frequently occurring worldwide, is very stable during food processing. Testing NX-3 at different pH-values and temperature conditions, as well as under conditions that simulate the storage of infected grains and bread-making process, revealed a strongly reduced stability of NX-3 and concurrent formation of NX3-M1. Although the NX-3 formed in planta is as toxic as DON, the extensive formation of the non-toxic rearrangement product should be taken into account for risk assessment of this emerging food contaminant.

Keywords: Alamar Blue assay; Detoxification; Fusarium graminearum; Sulforhodamine B assay; Trichothecene.

MeSH terms

  • Cell Survival / drug effects
  • Colon / cytology
  • Colon / drug effects
  • Edible Grain* / chemistry
  • Edible Grain* / microbiology
  • Food Contamination / analysis
  • Food Handling*
  • Food Microbiology
  • Food Storage
  • Fusarium / growth & development*
  • Fusarium / metabolism
  • HT29 Cells
  • Hot Temperature
  • Humans
  • Hydrogen-Ion Concentration
  • Molecular Structure
  • Structure-Activity Relationship
  • Trichothecenes* / chemistry
  • Trichothecenes* / isolation & purification
  • Trichothecenes* / toxicity

Substances

  • Trichothecenes
  • trichothecene NX-2