s Linz 2010 Altex 27, Suppl. 2/10 148 Lecture in Session VI: Acute and long term toxicity B Transcriptomic, proteomic and metabolomic alterations in RPTEC/TERT1 cells in response to Cyclosporine A Anja Wilmes 0, Lydia Aschauer 0, Alice Limonciel 0, Silke Ruzek 1, Andreas Handler 1, Christian Huber 1, Olga Schmal 2, Karin Herrgen 2, Christof Burek 2, Arno Lukas 3, Donatella Carpi 4, Claude Guillou 4, Philip Hewitt 5, Walter Pfaller 0 and Paul Jennings 0 Department of Physiology and Medical Physics, Medical University of Innsbruck (Innsbruck) (At); Faculty of Molecular Biology, Paris-lodron University (Salzburg) (At); Department of toxicology, University of Würzburg (Würzburg) (De); emergentec Biodevelopment GmbH (Vienna) (At); Institute For Health and Consumer Protection-Systems toxicology Unit, Joint Research Centre of the european Commission (Ispra) (It); Merck KGaA, Institute of toxicology (Darmstadt) (De) Contact: anja.wilmes@i-med.ac.at Cyclosporine A (CsA) remains one of the most widely used immunosuppressive drugs for use in organ transplantation; however, it is also associated with the development of chronic renal disease. While there is thought to be a vascular and glomerular component to CsA nephropathy, evidence shows that proximal tubular cells are also directly affected by this compound. In the present study we investigated the effect of long term repeat exposure of CsA on the human renal proximal tubule cell line RPTEC/TERT1. Cells were cultured to confluence on aluminium oxide, microporous supports and allowed to differentiate for two weeks prior to exposure. Cells were exposed to a fresh daily bolus of CsA at 5 or 15 μM for 1, 3 and 14 days. transepithelial electrical resistance (teeR) and lactate production were monitored on a daily basis. At each time point cells were harvested for transcriptomics, mass spectrometry based peptide profiling and NMR based metabolomics analysis. CsA exposure caused an increase in teeR of RPteC/teRt1 cells over the duration of the experiment, at both 5 and 15 μM. CsA also caused a sustained increase in glycolysis, as previously reported at 15 μM. transcriptomic analysis revealed the prominence of genes involved in cell cycle and p53 pathways. the effect of CsA on the RPteC/teRt1 proteome and metabolome was also demonstrated. We show here for the first time a full omics analysis of the effects of CsA in cultured renal epithelial cells. Hepatic drug toxicity is one of the leading causes of drug withdrawal from the market. While conventional 2D hepatocyte culture systems or suspension cultures are suitable for detection of acute toxicity, the assessment of subchronic to chronic hepatic toxicity requires models that allow prolonged maintenance of hepatocyte functionality. Based on a multi-compartment bioreactor technology for clinical bioartificial liver support (Schmelzer et al., 2009) we developed a miniaturised bioreactor prototype that allows 3D perfusion culture of liver cells in a capillary scaffold providing decentralised mass exchange and integral oxygenation. the device is based on the use of interwoven hollow fibre capillary