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Effect of thimerosal on Ca2+ movement and viability in human oral cancer cells.
- Source :
- Human & Experimental Toxicology; May2009, Vol. 28 Issue 5, p301-308, 8p, 7 Graphs
- Publication Year :
- 2009
-
Abstract
- The effect of thimerosal on cytosolic free Ca<superscript>2+</superscript> concentrations ([Ca<superscript>2+</superscript>]<subscript>i</subscript>) in human oral cancer cells (OC2) is unclear. This study explored whether thimerosal changed basal [Ca<superscript>2+</superscript>]<subscript>i</subscript> levels in suspended OC2 cells using fura-2. Thimerosal at concentrations between 1and 50 μM increased [Ca<superscript>2+</superscript>]<subscript>i</subscript> in a concentration-dependent manner. The Ca<superscript>2+</superscript> signal was reduced partly by removing extracellular Ca<superscript>2+</superscript>. Thimerosal-induced Ca<superscript>2+</superscript> influx was not blocked by L-type Ca<superscript>2+</superscript> entry inhibitors and protein kinase C modulators (phorbol 12-myristate 13-acetate [PMA] and GF109203X). In Ca<superscript>2+</superscript>-free medium, 50 μM thimerosal failed to induce a [Ca<superscript>2+</superscript>]<subscript>i</subscript> rise after pretreatment with thapsigargin (an endoplasmic reticulum Ca<superscript>2+</superscript> pump inhibitor). Inhibition of phospholipase C with U73122 did not change thimerosal-induced [Ca<superscript>2+</superscript>]<subscript>i</subscript> 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 Ca<superscript>2+</superscript> with the Ca<superscript>2+</superscript> 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 [Ca<superscript>2+</superscript>]<subscript>i</subscript> rises by causing phospholipase C-independent Ca<superscript>2+</superscript> release from the endoplasmic reticulum and Ca<superscript>2+</superscript> influx through non-L-type Ca<superscript>2+</superscript> channels. Thimerosal killed cells in a concentrationdependent manner through apoptosis. [ABSTRACT FROM AUTHOR]
- Subjects :
- CANCER cells
ORAL cancer
PHOSPHOLIPASES
PROTEIN kinases
PROTEIN kinase C
Subjects
Details
- Language :
- English
- ISSN :
- 09603271
- Volume :
- 28
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Human & Experimental Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 44255673
- Full Text :
- https://doi.org/10.1177/0960327109106548