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

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′-...

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Bibliographic Details
Published in:Food and chemical toxicology 2004-04, Vol.42 (4), p.619-624
Main Authors: Sundstøl Eriksen, G., Pettersson, H., Lundh, T.
Format: Article
Language:English
Subjects:
3T3 cells
Acetylation - drug effects
Acetyldeoxynivalenols
Animals
Biological and medical sciences
Biological Assay
BrdU bioassay
Bromodeoxyuridine - metabolism
cell culture
Chromatography, Gas
Cytotoxicity
de-epoxidation
De-epoxides
Deoxynivalenol
DNA
DNA - biosynthesis
DNA damage
dosage
Dose-Response Relationship, Drug
epoxides
fibroblasts
food contamination
Fusarium
Inhibitory Concentration 50
Medical sciences
metabolic detoxification
Mice
Mycotoxins
Mycotoxins - metabolism
Mycotoxins - toxicity
Nivalenol
Plant poisons toxicology
protein synthesis
secondary metabolites
small grains
Swiss 3T3 Cells - drug effects
Swiss 3T3 Cells - metabolism
toxicity testing
Toxicology
toxigenic strains
Trichothecenes
Trichothecenes - analysis
Trichothecenes - metabolism
Trichothecenes - toxicity
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Summary: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 μM). 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.
ISSN:0278-6915
1873-6351
DOI:10.1016/j.fct.2003.11.006