PMID- 19610678 OWN - NLM STAT- MEDLINE DCOM- 20100819 LR - 20161018 IS - 0730-7268 (Print) IS - 0730-7268 (Linking) VI - 28 IP - 12 DP - 2009 Dec TI - Pharmaceutical industry effluent diluted 1:500 affects global gene expression, cytochrome P450 1A activity, and plasma phosphate in fish. PG - 2639-47 LID - 10.1897/09-120.1 [doi] AB - Patancheru, near Hyderabad, India, is a major production site for the global bulk drug market. Approximately 90 manufacturers send their wastewater to a common treatment plant in Patancheru. Extraordinary high levels of a wide range of pharmaceuticals have recently been demonstrated in the treated effluent. As little as 0.2% of this effluent can strongly reduce the growth rate of tadpoles, but the underlying mechanisms of toxicity are not known. To begin addressing how the effluent affects aquatic vertebrates, rainbow trout (Oncorhynchus mykiss) were exposed to 0.2% effluent for 5 d. Several physiological endpoints, together with effects on global hepatic gene expression patterns, were analyzed. The exposed fish showed both an induction of hepatic cytochrome P450 1A (CYP1A) gene expression, as well as enzyme activity. Clinical blood chemistry analyses revealed an increase in plasma phosphate levels, which in humans indicates impaired kidney function. Several oxidative stress-related genes were induced in the livers; however, no significant changes in antioxidant enzyme activities or in the hepatic glutathione levels were found. Furthermore, estrogen-regulated genes were slightly up-regulated following exposure, and moderate levels of estriol were detected in the effluent. The present study identifies changes in gene expression triggered by exposure to a high dilution of the effluent, supporting the hypothesis that these fish are responding to chemical exposure. The pattern of regulated genes may contribute to the identification of mechanisms of sublethal toxicity, as well as illuminate possible causative agents. FAU - Gunnarsson, Lina AU - Gunnarsson L AD - Department of Neuroscience and Physiology, the Sahlgrenska Academy at University of Goteborg, Goteborg, Sweden. FAU - Kristiansson, Erik AU - Kristiansson E FAU - Rutgersson, Carolin AU - Rutgersson C FAU - Sturve, Joachim AU - Sturve J FAU - Fick, Jerker AU - Fick J FAU - Forlin, Lars AU - Forlin L FAU - Larsson, D G Joakim AU - Larsson DG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Environ Toxicol Chem JT - Environmental toxicology and chemistry JID - 8308958 RN - 0 (Estrogen Receptor alpha) RN - 0 (Industrial Waste) RN - 0 (Phosphates) RN - 0 (Water Pollutants, Chemical) RN - EC 1.14.14.1 (Cytochrome P-450 CYP1A1) SB - IM MH - Animals MH - Cytochrome P-450 CYP1A1/*metabolism MH - *Drug Industry MH - Estrogen Receptor alpha/genetics MH - Gene Expression Profiling MH - *Industrial Waste MH - Oligonucleotide Array Sequence Analysis MH - Oncorhynchus mykiss MH - Oxidative Stress MH - Phosphates/*blood MH - Water Pollutants, Chemical/*toxicity EDAT- 2009/07/21 09:00 MHDA- 2010/08/20 06:00 CRDT- 2009/07/21 09:00 PHST- 2009/03/13 00:00 [received] PHST- 2009/06/30 00:00 [accepted] PHST- 2009/07/21 09:00 [entrez] PHST- 2009/07/21 09:00 [pubmed] PHST- 2010/08/20 06:00 [medline] AID - 09-120 [pii] AID - 10.1897/09-120.1 [doi] PST - ppublish SO - Environ Toxicol Chem. 2009 Dec;28(12):2639-47. doi: 10.1897/09-120.1.