Cytotoxicity-related Alterations of Selected Cellular Functions After in Vitro Vanadate Exposure
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Pharmacology
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A bovine kidney cell line was used to monitor select cellular functions for toxicity-dependent alterations in an effort to examine the cellular response to vanadium insult. The vanadium concentrations utilized ranged between 20 and 500 microM Na3VO4 (V) and elicited 15-60% cytotoxicity. Cytotoxicity-related decreases in thymidine incorporation into DNA and leucine incorporation into protein were noted. Paradoxically, V-treated cultures exhibited increased protein and DNA content, suggestive of a decrease in precursor transport. K+-dependent phosphatase (KP), acid phosphatase (AP) and succinate dehydrogenase (SDH) were monitored in surviving cells and in a cell-free system. Significant inhibitions were detected for KP and AP; SDH exhibited slight enhancement. In the cell-free system, KP was inhibited significantly at 10(-7) M V, while AP and SDH were either unchanged or sensitive only at concentrations of 10(-4) M V or greater. Measurement of reduced glutathione (GSH) in surviving cells revealed toxicity-dependent increases of up to 500% of control values. When compared to the cellular V content, the GSH:V molar ratio decreased from 1.7 to 0.5 as cell survival decreased.
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