PMID- 20946947 OWN - NLM STAT- MEDLINE DCOM- 20110517 LR - 20191210 IS - 1879-3177 (Electronic) IS - 0887-2333 (Linking) VI - 25 IP - 1 DP - 2011 Feb TI - Precision-Cut Liver Slices of Salmo salar as a tool to investigate the oxidative impact of CYP1A-mediated PCB 126 and 3-methylcholanthrene metabolism. PG - 335-42 LID - 10.1016/j.tiv.2010.10.002 [doi] AB - Fish isolated cell systems have long been used to predict in vivo toxicity of man-made chemicals. In present study, we tested the suitability of Precision-Cut Liver Slices (PCLS) as an alternative to these models that allows the evaluation of a global tissue response to toxicants, to investigate oxidative stress response to cytochrome P450 1A (CYP1A) induction in fish liver. PCLS of Salmo salar were exposed for 21 h to increasing doses of 3-methylcholanthrene (3-MC) and Polychlorobiphenyl 126 (PCB 126). 3-MC (25 muM) strongly induced CYP1A transcription. In dose-response analysis (25-100 muM), EROD activity was strongly increased at intermediate 3-MC concentrations. We found the counter-intuitive decline of EROD at the highest 3-MC doses to result from reversible competition with ethoxyresorufin. No increases of H(2)O(2) production, antioxidant enzymes activities or oxidative damage to lipids were found with 3-MC treatments. PCLS subjected to PCB 126 (2-200 nM) showed increased contamination levels and a parallel increased CYP1A mRNA synthesis and EROD activity. H(2)O(2) production tended to increase but no oxidative damage to lipids was found. As antioxidant enzymes activities declined at the highest PCB 126 dose, it is suggested that longer incubation periods could be required to generate oxidative stress in PCLS. CI - Copyright (c) 2010 Elsevier Ltd. All rights reserved. FAU - Lemaire, Benjamin AU - Lemaire B AD - Institut des Sciences de la Vie, Universite catholique de Louvain, Louvain-la-Neuve, Belgium. FAU - Beck, Michael AU - Beck M FAU - Jaspart, Melanie AU - Jaspart M FAU - Debier, Cathy AU - Debier C FAU - Calderon, Pedro Buc AU - Calderon PB FAU - Thome, Jean-Pierre AU - Thome JP FAU - Rees, Jean-Francois AU - Rees JF LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Validation Study DEP - 20101012 PL - England TA - Toxicol In Vitro JT - Toxicology in vitro : an international journal published in association with BIBRA JID - 8712158 RN - 0 (RNA, Messenger) RN - 0 (Thiobarbituric Acid Reactive Substances) RN - 0 (Water Pollutants, Chemical) RN - 56-49-5 (Methylcholanthrene) RN - BBX060AN9V (Hydrogen Peroxide) RN - DFC2HB4I0K (Polychlorinated Biphenyls) RN - EC 1.- (Oxidoreductases) RN - EC 1.14.14.1 (Cytochrome P-450 CYP1A1) RN - EC 2.3.3.1 (Citrate (si)-Synthase) RN - TSH69IA9XF (3,4,5,3',4'-pentachlorobiphenyl) SB - IM MH - Animals MH - Citrate (si)-Synthase/metabolism MH - Cytochrome P-450 CYP1A1/*biosynthesis/genetics/metabolism MH - Enzyme Induction/drug effects MH - Hydrogen Peroxide/metabolism MH - Lipid Peroxidation/drug effects MH - Liver/chemistry/*drug effects/metabolism MH - Methylcholanthrene/*toxicity MH - Organ Culture Techniques MH - Osmolar Concentration MH - Oxidative Stress/*drug effects MH - Oxidoreductases/metabolism MH - Polychlorinated Biphenyls/analysis/*toxicity MH - RNA, Messenger/metabolism MH - Salmo salar MH - Thiobarbituric Acid Reactive Substances/metabolism MH - Time Factors MH - Toxicity Tests MH - Water Pollutants, Chemical/*toxicity EDAT- 2010/10/16 06:00 MHDA- 2011/05/18 06:00 CRDT- 2010/10/16 06:00 PHST- 2010/07/20 00:00 [received] PHST- 2010/09/30 00:00 [revised] PHST- 2010/10/04 00:00 [accepted] PHST- 2010/10/16 06:00 [entrez] PHST- 2010/10/16 06:00 [pubmed] PHST- 2011/05/18 06:00 [medline] AID - S0887-2333(10)00260-2 [pii] AID - 10.1016/j.tiv.2010.10.002 [doi] PST - ppublish SO - Toxicol In Vitro. 2011 Feb;25(1):335-42. doi: 10.1016/j.tiv.2010.10.002. Epub 2010 Oct 12.