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(07-06) Assessment of toxicological modes of action of chemicals: from conventional biomarkers to toxicogenomics. De Coen, Wim*,1, Moens, Lotte1, Van der Ven, Karlijn1, Hoff, Philippe1, Caturla-Goni, Mercè1, Vlaeminck, Andrea1, Dardenne, Freddy1, Willems, Kris1, Blust, Ronny1, 1 University of Antwerp, Groenenborgerlaan 171, Antwerp, Antwerp, Belgium ABSTRACT- Biomarkers have since long been used to characterise suborganismal effects of chemicals and have been proposed as tools to assess the toxicological modes of action of chemicals. The advent of toxicogenomics, however, has made it possible to obtain more discriminatory power in distinguishing molecular mechanisms of chemicals. In the present study, two different methods for gene-expression analysis will be discussed to demonstrate their usefulness in ecotoxicological research. Cell-based transcription profiling using transgenic assays with pro-and eukaryotic cells has been applied to document the toxicological mode of action of perfluorinated chemicals. Recent findings have shown that these chemicals (with perfluorooctane sulfonic acid as the most important representative) are detected in industrialized as well as arctic regions, and accumulate preferentially in the liver and blood of wildlife species. To further document the potential hazard associated with these compounds we used cellular receptor-reporter assays with E. coli and human liver cells to illustrate the effects caused by these toxicants (e.g. membrane-perturbation, DNA damage and oxidative stress). A second technique offering more insight into mechanisms of toxicity are DNA arrays. Until now, however, a major drawback is the limited availability of DNA arrays for relevant ecotoxicological test species. We therefore developed our own cDNA array for carp to detect the endocrine disruptive effects of chemicals. Based on gender-specific cDNA libraries relevant information is gathered on the impact of chemicals on the reproductive axis. Futher examples of these toxicogenomic tools will be given to document the neuro-endocrine effects of neurofarmaca on zebrafish and to elucidate the potential mechanisms of perfluorinated chemicals on the same test species. The limitations, advantages as well as the relationship with parameters at higher levels of biological organisation will be discussed for these promising ecotoxicological tools. Key words: Biomarkers, Toxicogenomics, PFOS |
