Effects of Specific Inhibitors of Cellular Functions on Sulfur Mustard-InducedCell Death

摘要

This study was conducted to determine whether inhibitors of normal cellularfunctions can reduce cytotoxicity induced by sulfur mustard (HD). The compounds examined include inhibitors of poly(ADP-ribose) polymerase (PADPRP), inhibitors of mono(ADP-ribose) transferase (MADPRT), inhibitors of lipid peroxidation, and an inhibitor of protein synthesis. To determine the effects of these compounds on HD-induced cell death, human lymphocyte preparations were treated with known concentrations (0.1 pM to 1000 pAl) of an inhibitor and exposed to an estimated 87% effect concentration (EC87) of HD (170 pM) for loss in cell viability. Cell viability was determined at 24-26 hr post-exposure to HD using a dye (propidium iodide) exclusion assay and a flow cytometer. All of the selected PADPRP inhibitors were found to be effective at reducing the cytotoxic effects of HD. These inhibitors were rank-ordered based on the concentration that gives 50% (EC50) reduction of HD-induced cell death. A significant correlation (r = 0.94) was observed between the compounds' ability to inhibit PADPRP and the compounds'