Toxicological characterization of selected secondary fungal metabolites in Norwegian grain

Grains are commonly infected with toxigenic fungi, particularly with species of the Fusarium and Alternaria genera. Fusarium fungi are producers of a range of well known mycotoxins as well as less known bioactive metabolites for which little toxicological information exists. Food and feed containing naturally infected cereals have often more pronounced effects in animals than if the corresponding levels of pure trichothecenes are added to the feed. This may be due to the presence of other fungal metabolit es. The aim of this project is to provide a toxicological characterization of selected cytotoxic fungal metabolites other than trichothecenes present in Norwegian grains, and to assess their contribution to the toxicity of grains contaminated with toxigen ic field fungi. Selected metabolites from Fusarium will be purified for further studies. The selected cytotoxic metabolites will be further studied in appropriate cell models(s) to provide information about toxicity and cellular targets, and the effects w ill be compared to those of trichothecenes. The information obtained will also be study the combined effect of selected cytotoxic compounds. The effects of these fungal metabolites on gene expression will be studied by microarray technology and the effect s on gene expression will be related to observations from the cellular systems. An in vivo study will be performed to sustain that the in vitro findings also apply to intact organisms. The information generated on mechanisms of action will be used to clar ify the role of different metabolites in the toxicity of Fusarium infected grain and thereby strengthen the hazard identification and hazard characterization to improve the risk assessment of mycotoxins in cereals.