Effect of thimerosal on Ca2+ movement and viability in human oral cancer cells.

The effect of thimerosal on cytosolic free Ca²⁺ concentrations ([Ca²⁺]_i) in human oral cancer cells (OC2) is unclear. This study explored whether thimerosal changed basal [Ca²⁺]_i levels in suspended OC2 cells using fura-2. Thimerosal at concentrations between 1and 50 μM increased [Ca²⁺]_i in a concentration-dependent manner. The Ca²⁺ signal was reduced partly by removing extracellular Ca²⁺. Thimerosal-induced Ca²⁺ influx was not blocked by L-type Ca²⁺ entry inhibitors and protein kinase C modulators (phorbol 12-myristate 13-acetate [PMA] and GF109203X). In Ca²⁺-free medium, 50 μM thimerosal failed to induce a [Ca²⁺]_i rise after pretreatment with thapsigargin (an endoplasmic reticulum Ca²⁺ pump inhibitor). Inhibition of phospholipase C with U73122 did not change thimerosal-induced [Ca²⁺]_i rises. At concentrations between 5 and 10 μM, thimerosal killed cells in a concentration-dependent manner. The cytotoxic effect of 8 μM thimerosal was potentiated by prechelating cytosolic Ca²⁺ with the Ca²⁺ chelator 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetate/acetomethyl (BAPTA/ AM). Flow cytometry data suggested that 1-7 μM thimerosal-induced apoptosis in a concentrationdependent manner. Collectively, in OC2 cells, thimerosal-induced [Ca²⁺]_i rises by causing phospholipase C-independent Ca²⁺ release from the endoplasmic reticulum and Ca²⁺ influx through non-L-type Ca²⁺ channels. Thimerosal killed cells in a concentrationdependent manner through apoptosis. [ABSTRACT FROM AUTHOR]