Sulfur Mustard-Induced Apoptosis in Hairless Guinea Pig Skin

Abstract

Sulfur mustard [bis-(2-chloroethyl)sulfide; HD] causes incapacitating injuries to the eyes, respiratory tract, and skin. Despite decades of research, the mechanism of toxic action of HD is still poorly understood. One proposed toxicological mechanism that triggers cell death involves DNA damage induced by HD alkylation. According to this hypothesis, HD-induced DNA damage activates NAD+, requiring the enzyme poly(ADP-ribose) polymerase (PARP) to initiate DNA repair processes. Overactivation of PARP leads to depletion of NAD+, and, in efforts to resynthesize NAD+, cellular ATP is depleted, and the cell dies from intracellular energy. However, recent studies only partial support this hypothesis. Niacinamide, a substrate for NAD+ synthesis, prevented NAD+ depletion, but did not significantly prevent cell death following HD exposure. These studies suggest cell death occurs independently of depletion of cellular NAD+ with some other pathogenic processes operating in cell death following HD cytotoxicity.The present study examined the role of apoptosis in basal cell degeneration caused by HD exposure in the hairless guinea pig.