Use of pro- and eukaryotic stress gene assays to characterise mode of action of chemicals and detect environmental contaminants

Anthropogenic as well as naturally occurring contaminants are present in our environment, for example mycotoxins and pesticides are typical food contaminants, metals and pesticides are common polluters of water and sediment. To determine the potential hazards of the individual compounds and mixtures and evaluate their toxicity different types of tests have been developed. In recent years advances in the use of in vitro cellular systems made it possible to characterise events at one of the earliest levels of molecular responses: gene expression. This research project uses E. coli and a human liver cell based stress gene profiling assays to determine the effect of chemicals and mixtures thereof on stress gene activation. The stress promoters used in these assays control transcription of genes involved in stress-related processes such as DNA damage, oxidative stress, osmotic stress, protein perturbation and tumour induction.
These assays can reveal whether or not a substance is potentially toxic, and provide information concerning the nature or mode of action of the toxicants present.

In a recent study on food contaminants we compared different pure chemicals like mycotoxins, glyphosate paraquat and other pesticides. Each toxicant generates a unique fingerprint of the mode of action. After grouping the profiles according to their mode of action, we challenged our databank to position extracts of contaminated food samples next to their toxicologically similarly acting relatives. In this way evaluating the possible use of the assays for rapid screening of contaminants in food extracts. Results show that for example different commercial forms of glyphosate show different dose response profiles probably caused by the different surfactants used.