Comparative in vitro effects of sodium arsenite and sodium arsenate on neuroblastoma cells.
The toxic effects of arsenic at different cellular levels were assessed using two inorganic chemical species: sodium arsenite and sodium arsenate, representing the trivalent and pentavalent states of arsenic, respectively. Mouse neuroblastoma cell cultures (Neuro-2a) were exposed for 24 h, and cytotoxic effects evaluated were: cell proliferation by quantification of total protein content; cytoplasmic membrane integrity to cytosolic lactate dehydrogenase leakage; lysosomal hexosaminidase release; lactate dehydrogenase activity; mitochondrial succinate dehydrogenase activity; relative neutral red uptake by lysosomes; lysosomal hexosaminidase sphingolipid degradation activity; and acetylcholinesterase activity. As(III) was found to be five times more toxic than As(V) to neuroblastoma cell proliferation, but the relative extent of other alterations differed. Special sensitivity was detected for lactate dehydrogenase inhibition. Hexosaminidase activity was also very susceptible, being inhibited at low concentrations and stimulated at high concentrations. Less sensitive were the inhibition of cell proliferation, relative neutral red uptake, and acetylcholinesterase activity. As(III) was lysosomotropic, with secretion of hexosaminidase, but the release was decreased by As(V). Mitochondrial succinate dehydrogenase was inhibited by As(III) and stimulated by As(V). Minor sensitivity to cytoplasmic lactate dehydrogenase leakage for both compounds also shows that functional metabolic alterations produced by arsenic are more important than structural damage.
Repetto
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National Institute of Toxicology, Sevilla, Spain.
Sanz
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Repetto
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D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001149:Arsenates / Q000633:toxicity*; D018053:Arsenites / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D017670:Sodium Compounds / Q000633:toxicity*; D013107:Sphingolipids / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000378:metabolism; D014407:Tumor Cells, Cultured; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D001149:Arsenates; D018053:Arsenites; D017670:Sodium Compounds; D013107:Sphingolipids; C017947:sodium arsenite; C009277:sodium arsenate; D007770:L-Lactate Dehydrogenase; D013385:Succinate Dehydrogenase; D000110:Acetylcholinesterase; D001619:beta-N-Acetylhexosaminidases