Characterization of epidermal and dermal remodeling following skin injury by sulfur mustard in Göttingen minipigs.

PURPOSE: Sulfur mustard (SM) is a highly reactive chemical warfare agent that causes severe cutaneous injury, including blistering, necrosis, inflammation, and delayed wound repair. This exploratory study characterized cellular and molecular changes associated with SMinduced skin injury and repair over 60 days.

MATERIALS AND

METHODS

Göttingen minipigs received a single SM exposure using a vapor cap model. Skin samples were analyzed for changes in epidermal architecture, proliferation, adhesion, differentiation, and dermal remodeling using histopathology and immunochemistry. Markers included proliferating cell nuclear antigen (PCNA), E-cadherin, keratin 10, and loricrin. Trichrome staining assessed collagen organization and extracellular matrix remodeling.

RESULTS

At 2 days post exposure, marked epidermal disruption, including degeneration and necrosis of basal and suprabasal keratinocytes, was accompanied by mild dermal edema and polymorphonuclear leukocyte infiltration. From 9 to 28 days, epidermal repair was evident, with hyperplasia, irregular stratification, and incomplete differentiation of the neoepidermis. Increased PCNA expression indicated enhanced basal keratinocyte proliferation, while reduced E-cadherin expression suggested impaired epithelial adhesion. Altered keratin 10 and loricrin localization demonstrated disrupted keratinocyte differentiation and barrier formation. Trichrome staining demonstrated dermal remodeling, including mild edema, increased cellularity, and the development of a distinct papillary-reticular interface. By 60 days, partial restoration of epidermal organization and normalization of keratin expression suggested progressive recovery.

CONCLUSIONS

SM exposure induces persistent alterations in epidermal architecture, proliferation, differentiation, adhesion, and dermal matrix organization. These findings provide preliminary insight into mechanisms underlying SM-induced skin injury and repair and support further investigation of pathways regulating epidermal regeneration and dermal remodeling.