Hamilton, M.G., F. M. Dorandeu, M. McCaffery, P.M. Lundy and T. W. Sawyer. Modification of Cytosolic Free Calcium Concentrations in Human Keratinocytes after Sulfur Mustard Exposure. Toxic. in Vitro 1998. 12: 365-372.

sulfur mustard - 00505-60-2

Exposure of confluent cultures of human skin keratinocytes to sulfur mustard (SM) induced an immediate and irreversible rise in internal free Ca²⁺ levels that was independent of external Ca²⁺ concentrations. The response was rapid, beginning within 1 min after addition of SM to the cells, and sensitive, with significant effects observed at 100 uM. The rise in [Ca²⁺]_INT was unaffected by zero external Ca²⁺ but was blocked by prior incubation with thapsigargin. The sensitivity to and irreversibility of the effects of SM on Ca²⁺ levels was paralleled by cellular toxicity as assessed using three different cell viability assays. In addition, the time course of the onset of irreversible toxicity in our cultures coincides with the time course of effects on [Ca²⁺]_INT. SM was also found to displace specifically bound ATP from purinergic (P₂) receptors. These results suggest that therapies aimed at protecting internal stores of Ca²⁺ from disruption by SM, perhaps at P₂ receptors, may provide substantial benefit in protecting human skin cells from the toxic effects of this vesicant.