Smith, E.M., A.G. McArthur, M. Galus, S. Higgins, N. Kirischian, J. Jeyaranjaan, & J.Y. Wilson. 2011. Transcriptional responses of zebrafish to chronic, low-dose pharmaceutical exposure. Oral presentation at the 16th International Symposium on Pollutant Response in Marine Organisms, Long Beach, California.Human pharmaceuticals have been well documented in receiving waters yet their impacts on aquatic species are not clear. We have exposed adult zebrafish for 6 weeks to waterborne acetaminophen, gemfibrozil, venlafaxine, and carbamazepine at two doses (0.5 and 10 μg L-1) and assessed hepatic transcriptional responses using a commercial microarray. These four pharmaceuticals have been frequently found in wastewater effluent and receiving waters. For all compounds, reproduction was significantly reduced and histopathological changes induced in kidney with at least the 10 μg L-1 exposure. Livers were pooled to provide sufficient RNA for microarray and qPCR analyses. Gene expression was determined with a modified Agilent 44K zebrafish microarry using a single channel approach. Significantly different probes were identified with a 2-way ANOVA (sex and treatment) and rank product analyses with a 10% false discovery rate. Transcriptional responses were particularly marked with acetaminophen exposure and there was broad overlap in the significant probes found between doses and across gender for this compound. 52 probes were at least 20 fold up- or down- regulated in acetaminophen exposed fish; 3 probes (LIST) had 100 fold up- or down- regulated. Venlafaxine responses were few in males and carbamazepine impacted hepatic transcription the least in both sexes. There was a strong sex dependant response to both venlafaxine and carbamazepine. Unique probes were identified for all exposures suggesting a unique transcriptional response may occur for each pharmaceutical. The biological relevance of these exposures is being explored through analysis of enriched GO terms, metabolic pathways and interactome networks.
