Cytotoxic effects of triphenylbismuth on rat thymocytes: comparisons with bismuth chloride and triphenyltin chloride

The biomedical and industrial uses of organobismuth compounds have become widespread, although there is limited information concerning their cytotoxicity. Therefore, the actions of triphenylbismuth on rat thymocytes were examined using a flow cytometer with ethidium bromide, annexin V-FITC, fluo-3-AM, and 5-chloromethylfluorescein (5CMF) diacetate. Triphenylbismuth at 3-30 microM increased the population of cells stained with ethidium, indicating a decrease in cell viability. Organobismuth at 30 microM increased the population of cells positive to annexin V, suggesting an increase in the population of apoptotic cells. Triphenylbismuth at 3 microM or more decreased cellular glutathione content (5CMF fluorescence intensity) and increased intracellular Ca(2+) concentration ([Ca(2+)](i), fluo-3 fluorescence intensity) in a dose-dependent manner. Because an increase in [Ca(2+)](i) is linked to cell death or cell injury and a decrease in cellular glutathione content increases cell vulnerability to oxidative stress, the triphenylbismuth-induced changes in cellular parameters may be responsible for triphenylbismuth-induced cytotoxicity. Bismuth chloride at 10-30 microM did not significantly affect cell viability. These results suggest that triphenylbismuth at micromolar concentrations exerts cytotoxic action on rat thymocytes, possibly related to a health hazard. Although the cytotoxicity of triphenylbismuth was less than that of triphenyltin, one of the environmental pollutants, it is necessary to direct our attention to the use and disposal of organobismuth compounds.