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

摘要

The effect of HD on cell death was examined in a variety of tests in a number of phylogenetically distinct cell types. HD caused concentration dependant apoptosis with increasing numbers of necrotic cells at higher concentrations. A variety of techniques were used to examine HD induced cellular biochemical responses in attempts to identify a critical determinant of initiation of these events. Much of the work describes attempts to relate HD induced changes in intracellular calcium levels with cell death and also to determine the role of cell surface ionotropic ATP receptors (calcium pores), which when stimulated might be responsible for the calcium influx since upon stimulation they mimicked many of the apoptotic effects of HD. Examination of the intracellular biochemical events known to be related to induction of apoptosis such as the role of certain caspases and DNA were also carried out. Some studies describe the characterization of a cytolytic pore complex in certain cells and the effects of HD on this pore. Other studies were prompted by our initial findings of the importance of cationic environment on ATP toxicity. This work identified the extreme importance of ionic environment (including pH) on HD toxicity.