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 ?1/4M 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 ?1/4M thimerosal failed to induce a [Ca ²⁺]_i rise after pretreatment with thapsigargin (an endoplasmic reticulum Ca²⁺ pump inhibitor). Inhibition of phospholipase C with U73122 did not change thimerosal-induced [Ca ²⁺]_i rises. At concentrations between 5 and 10 ?1/4M, thimerosal killed cells in a concentration-dependent manner. The cytotoxic effect of 8 ?1/4M thimerosal was potentiated by prechelating cytosolic Ca ²⁺ with the Ca²⁺ chelator 1,2-bis(2-aminophenoxy)ethane-N, N,Nĝ€2,Nĝ€2-tetraacetate/acetomethyl (BAPTA/ AM). Flow cytometry data suggested that 1g-7 ?1/4M thimerosal-induced apoptosis in a concentration-dependent 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 nong-L-type Ca²⁺ channels. Thimerosal killed cells in a concentration-dependent manner through apoptosis.