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1H c (1) - Pharmaceuticals (WE6/13) Development of gene expression-based assays for detection of neurotoxic effects of pharmaceuticals in zebrafish (Danio rerio). Van der Ven, Karlijn1, Moens, Lotte1, Blust, Ronny1, De Coen, Wim1, 1 Laboratory for Ecophysiology, Biochemistry and Toxicology, Antwerp, Antwerp, Belgium ABSTRACT- With the growing awareness of the occurrence of human and veterinary pharmaceuticals in aquatic ecosystems, the environmental concentrations and possible effects of drugs in the environment has become more and more a subject of public concern. Although a great variety of pharmaceuticals has already been detected in the aquatic environment, very little is currently known about their effect on non-target organisms. Since gene expression can be considered as the basis of all toxicological responses, the use of cDNA-arrays is a good method to detect toxic effects in a fast and sensitive way. At present we are evaluating the effects of pharmaceuticals in teleosts as models of aquatic non-target species. In a first phase sensitive analytical methods have been developed for the detection of several pharmaceuticals (diazepam, chlorpromazine, mianserin) in environmental water samples and for the assessment of exposures to these pharmaceuticals under controlled laboratory conditions. Secondly gene expression analysis in the brain of zebrafish ( Danio rerio ), exposed to these model neuropharmaceuticals and 17-b-estradiol has been performed using tissue specific cDNA clone arrays. In addition, we evaluated the gene expression profile of specific genes known to be involved in important neurological and/or endocrine pathways using dot-blot hybridization (e.g. tyrosine hydroxylase, glutamic acid decarboxylase, dopamine-b-hydroxylase). These hybridization experiments provided mechanism-based information on the mode of action of these chemicals. Those genes that generated compound-specific expression profiles were evaluated as possible new biomarkers for the impact assessment of pharmaceuticals on fish populations. Key words: Biomarkers, Pharmaceuticals, Toxicogenomics, Zebrafish |
