Ultrastructural Correlates of Sulfur Mustard Toxicity

Abstract

Standardized ultrastructural technology was used to study subcellular effects of sulfur mustard (HD) on human lymphocytes in vitro, human keratinocytes in culture, and the skin of the hairless guinea pig. While dosages of mustard differed according to the dictates of individual protocols, all specimens were gathered 24 hr following exposure, aldehyde-fixed, and processed for transmission and scanning electron microscopic examination. In the hairless guinea pig model, the subcellular effects on basal cells of the stratum genninativum and the generation of microblisters at the dermal-epidermal junction were unequivocal to that reported for human skin grafted to congenitally athymic nude mice. Basal cell degenerative changes, signaled by nuclear condensations, blebbing of the perinuclear envelope, and defects of the plasmalemma, progressed to paranuclear cytoplasmic vacuolations, loss of cellular organelles, lipid inclusions, increased lysosomal activity, and necrosis. Boundaries of the microblister, components of the roof and floor of the blister cavity, and apparent disabling of anchoring filaments of hemidesmosomes in the formation of the microblister were also similar. In human lymphocytes in vitro and human keratinocytes in culture, HD-induced pathologic changes were identical to those of the basal cell of the skin models. Nuclear chromatin condensations, nuclear envelope blebbing, and interruptions of the plasmalemma were again persistent temporal ultrastructural features of the cascading cellular pathologic appearance of HD-induced toxicity. It is expected that establishing and comparing ultrastructural correlates of HD toxicity in differing model systems will provide a useful morphologic database against which prophylactic and therapeutic regimens might be measured.