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Reprod Toxicol ; 23(4): 513-20, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17367990

RESUMO

The trophoblast cell line, JEG-3, was used to study the cytotoxicity of phenanthrene, 9,10-phenanthrenequinone (PHEQ), anthracene, and 9,10-anthracenedione alone and with copper. The endpoints were the capacity of cultures to reduce alamar Blue (AB), a measure of energy metabolism, and to convert carboxyfluorescein diacetate acetoxymethyl ester (CFDA AM) to carboxyfluorescein, an indication of membrane integrity. Only PHEQ elicited a cytotoxic response. PHEQ caused a concentration-dependent decline in AB but not in CFDA AM readings, suggesting an impairment to energy metabolism. In the presence of copper, PHEQ concentration-response curves were shifted to the left for AB and were obtained with CFDA AM. The Cu/PHEQ synergy is attributed to an increase in redox cycling and production of reactive oxygen species (ROS), which overwhelm antioxidant defenses, damaging energy metabolism first and then membrane integrity. The impermeable copper chelator, bathocuproine, reduced the PHEQ/copper interaction, but the permeable chelator, neocuproine, and copper together were cytotoxic.


Assuntos
Cobre/toxicidade , Poluentes Ambientais/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Fenantrenos/toxicidade , Placenta/efeitos dos fármacos , Trofoblastos/efeitos dos fármacos , Antracenos/toxicidade , Antraquinonas/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quelantes/toxicidade , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Metabolismo Energético/efeitos dos fármacos , Humanos , Oxirredução , Fenantrolinas/toxicidade , Placenta/metabolismo , Placenta/patologia , Espécies Reativas de Oxigênio/metabolismo , Trofoblastos/metabolismo , Trofoblastos/patologia
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