Modification of cytosolic free calcium concentrations in human keratinocytes after sulfur mustard exposure

Toxicology in Vitro : an International Journal Published in Association with BIBRA
M G HamiltonT W Sawyer

Abstract

Exposure of confluent cultures of human skin keratinocytes to sulfur mustard (SM) induced an immediate and irreversible rise in internal free Ca(2+) levels that was independent of external Ca(2+) concentrations. The response was rapid, beginning within 1min after addition of SM to the cells, and sensitive, with significant effects observed at 100 mum. The rise in [Ca(2+)](INT) was unaffected by zero external Ca(2+) but was blocked by prior incubation with thapsigargin. The sensitivity to and irreversibility of the effects of SM on Ca(2+) 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 [Ca(2+)](INT). SM was also found to displace specifically bound ATP from purinergic (P(2)) receptors. These results suggest that therapies aimed at protecting internal stores of Ca(2+) from disruption by SM, perhaps at P(2) receptors, may provide substantial benefit in protecting human skin cells from the toxic effects of this vesicant.

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Citations

May 4, 2000·Toxicology in Vitro : an International Journal Published in Association with BIBRA·T W Sawyer, M G Hamilton
Aug 26, 1998·Toxicology and Applied Pharmacology·T W SawyerP A D'Agostino
Apr 2, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Mahsa Zarei, T Shivanandappa
Feb 20, 2016·Journal of Basic and Clinical Physiology and Pharmacology·Mahsa Zarei, T Shivanandappa
Oct 3, 2019·Critical Reviews in Toxicology·Leila EtemadMahdi Balali-Mood
May 8, 2007·Toxicology and Applied Pharmacology·Thomas W SawyerAndrew Burczyk

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