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Toxicol In Vitro ; 25(1): 335-42, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20946947

RESUMEN

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 µM) strongly induced CYP1A transcription. In dose-response analysis (25-100 µM), 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.


Asunto(s)
Citocromo P-450 CYP1A1/biosíntesis , Hígado/efectos de los fármacos , Metilcolantreno/toxicidad , Estrés Oxidativo/efectos de los fármacos , Bifenilos Policlorados/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Citrato (si)-Sintasa/metabolismo , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Inducción Enzimática/efectos de los fármacos , Peróxido de Hidrógeno/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/química , Hígado/metabolismo , Técnicas de Cultivo de Órganos , Concentración Osmolar , Oxidorreductasas/metabolismo , Bifenilos Policlorados/análisis , ARN Mensajero/metabolismo , Salmo salar , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Factores de Tiempo , Pruebas de Toxicidad
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