Mediation of Sulfur Mustard Cellular Toxicity by ATP: A Possible Mechanism of Action of Sulfur Mustard Toxicity.

摘要

Following exposure to the P2X7 receptor agonist benzyl ATP (BzATP) or to HD, CHO-K 1 cells underwent cell death which was largely apoptotic in nature. The toxicity was very dependant on the ionic composition of the incubation medium. Inhibition of the P2X7 receptor by oxidized ATP (oATP) blocked BzATP induced cytotoxicity but appeared only to shunt HD induced cell death from apoptosis (as measured by a variety of techniques) to necrosis. A membrane bound, cytolytic pore complex was identified in CHO-K1 cells which consisted of two separate receptors coupled to a cytolytic pore. Agonists of the two receptors, factors controlling the activation of the cytolytic pore and the fate of the cell following pore activation were examined. Initial studies concerning the interactions of HD with various constituents of the complex were carried out. HD under the conditions employed to date did not activate the pore directly nor did it promote activation of the P2X7 receptor but studies are ongoing. An extensive study of the role of calcium in MD induced cell death was continued indicating that calcium appears to be necessary for apoptosis but not cell death. A very important role for ions in MD induced cell death was identified.