http://worldcat.org/entity/work/id/195778472

DNA Damage-Induced Apoptosis: Inhibition by Calmodulin Antagonist, Fas Receptor Antibody and Caspase Inhibitors

Sulfur mustard (HD, bis-(2-chloroethyl) sulfide) is a vesicant that causes DNA strand breaks and apoptosis in cultured normal human epidermal keratinocytes (NHEK). HD causes apoptosis via two independent pathways, a Ca2+/calmodulin (CaM)-mediated mitochondrial pathway and Fas receptor (CD95) pathway. We studied the effects of the exogenously added CaM antagonist W7, the CD95 antibody, the caspase-3 inhibitor Ac-DEVD-CHO, and the general caspase inhibitor Z-VAD-fmk on NHEK viability loss (Calcein AM fluorescence assay, LDH release assay) due to HD. All protected against HD. Z-VAD-fmk was the most effective. These results provide a logical approach toward developing an anti-apoptotic vesicant countermeasure.

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