Mediation of Sulfur Mustard Cellular Toxicity by ATP: A Possible Mechanism of Action of Sulfur Mustard Toxicity
Abstract
HD caused apoptosis and to a lesser degree, necrosis in a wide variety of cell types. As the concentration of HD was increased the proportion of necrotic cells became more predominant. HD produced a modest elevation of intracellular calcium levels in J774 and CHO-Kl cells, as well as in human skin keratinocytes, although this rise did not seem causally related to HD induced cell death. However, very recent evidence indicates that HD induced DNA fragmentation may not he directly related to cytotoxicity. HD also activated caspase-3 in CHO-K1 cells, but neither specific nor general caspase inhibitors nor proteosome inhibitors reduced HD cytotoxicity. These results suggest that the toxicity of HD is fundamentally different than apoptotic stimulae such as dexamethasone or X-irradiation, in which the apoptosis induced by both of these treatments can he reduced by the above mentioned protease inhibitors. Subtypes of the P2X(sub 7) receptors were identified in neuronal synaptosomes, J774 cells and CHO-Kl cells. In CHO-K1 cells P2X(sub 7) receptor subtypes were identified and the specific P2X(sub 7) inhibitor, oxidized ATP, was found effective in reducing HD induced DNA fragmentation and the appearance of soluble DNA. However, this treatment appeared only to shunt the mechanism of cell death from being predominantly apoptotic, to more necrotic in nature; however, the overall cytotoxicity remained unchanged.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2000
- Accession Number
- ADA387203
Entities
People
- Paul Lundy