Pathology Produced by Sulfur Mustard in Human Skin Grafts on Athymic Nude Mice. II. Ultrastructural Changes

Abstract The human skin graft/nude mouse model was used to study sulfur mustard (SM) -induced pathology of skin at the ultrastructural level. The electron microscope confirms and extends the histopathology previously noted under light microscopy. SM caused extensive injury to the basal keratinocytes, the severity of which was dependent on both time and dose. Ultrastructurally visible damage took several hours to develop. The following sequence of morphological changes was observed: (a) Extensive condensation and margination of heterochromatin and loss of euchromatin, (b) blebbing of the nuclear membrane, (c) appearance of perinuclear vacuoles, (d) swelling of the endoplasmic reticulum, (e) progressive dissociation of rosettes of free polyribosomes, (f) formation of cytoplasmic vacuoles, (g) loss of the integrity of the basal cell plasma membrane, (h) leakage of cell contents and debris into the lamina lucida, (i) disruption of the anchoring filaments of hemidesmosomes with separation of the plasma membrane from the lamina densa, and accumulation of edema fluid in the lamina lucida, and (j) infiltration of phagocytes into areas of major damage. The damage to the basal cell layer eventually resulted in the separation of the epidermis from the dermis and the formation of a subepidermal microblister. Changes in the dermis were also noted, but these did not become evident until after basal cell injury was already underway. The dermal changes consisted of edema with separated but otherwise intact collagen bundles, and of damage to the fibroblasts and endothelial cells which were in close proximity to the necrotic basal cell layer. The pathology observed at the ultrastructural level strongly supports the view that the SM-induced injury to human skin begins at the basal cell layer.