Comparative effects of the metabolic inhibitors 2,4-dinitrophenol and iodoacetate on mouse neuroblastoma cells in vitro.
The toxic effects of two metabolic inhibitors, dinitrophenol and iodoacetic acid, were compared. Mouse neuroblastoma cell cultures (Neuro-2a) were exposed to different concentrations of the toxic compounds for 24, 48 and 72 h to study basal toxicity effects (cell proliferation by quantification of total protein content (PR) and relative neutral red uptake (RNRU) by lysosomes). The following biochemical indicators assessed in the in vitro test system were: cytosolic phosphofructokinase (PFK) and enolase (ENL) activities in glycolysis; mitochondrial succinate dehydrogenase (SDH) activity in the citric acid cycle; lysosomal beta-galactosidase (GAL) activity; and neuronal acetylcholinesterase (AChE) activity. The effects of the two metabolic inhibitors on the various indicators differed. Iodoacetic acid was found to be far more toxic than dinitrophenol to neuroblastoma cell proliferation at 24 h exposure. Though 2,4-dinitrophenol and iodoacetic acid both inhibited cell proliferation of the neuroblastoma cells, their effects on the other endpoints were opposite. Dinitrophenol was a general activator of the metabolism, particularly affecting lysosomal function. Iodoacetic acid did not significantly alter general metabolism, but considerably modified lysosomal function and AChE activity. The modification of lysosomal function of Neuro-2a cells by the two compounds was quite different: dinitrophenol increased RNRU and GAL activity, and iodoacetic acid decreased both parameters.
Andrés
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MI
National Institute of Toxicology, Seville, Spain.
Repetto
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G
Sanz
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Repetto
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D019297:2,4-Dinitrophenol; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004140:Dinitrophenols / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006019:Glycolysis / Q000187:drug effects; D007461:Iodoacetates / Q000633:toxicity*; D019807:Iodoacetic Acid; D007928:Lethal Dose 50; D008247:Lysosomes / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D009447:Neuroblastoma / Q000473:pathology*; D009474:Neurons / Q000201:enzymology; D009499:Neutral Red / Q000378:metabolism; D010732:Phosphofructokinase-1 / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014475:Uncoupling Agents / Q000633:toxicity*; D001616:beta-Galactosidase / Q000378:metabolism
D004140:Dinitrophenols; D007461:Iodoacetates; D014475:Uncoupling Agents; D009499:Neutral Red; D010732:Phosphofructokinase-1; D000110:Acetylcholinesterase; D001616:beta-Galactosidase; D010751:Phosphopyruvate Hydratase; D019297:2,4-Dinitrophenol; D019807:Iodoacetic Acid