Effects of Nicotinamide on Biochemical and Morphological Changes Induced bySulfur Mustard in Human Skin Organ Cultures

摘要

Blister formation due to sulfur mustard (HD) exposure was studied in an ex vivohuman skin model. Pieces of fresh human skin were exposed to HD vapor and subsequently incubated in medium for 48 hr. During the culture period cellular NAD+ levels and uptake of glucose from the medium decreased relative to the duration of the exposure to HD. In light microscopic sections of skin that was exposed to HD for 6 min, clefts of variable size could be clearly observed between epidermis and dermis after a 48 hr culture period. Immunohistochemical staining of collagen type IV demonstrated that separation occurred between the basal membrane and the basal keratinocytes. Since it was reported that nicotinamide could protect cellular NAD+ levels after HD exposure, HD-treated skin pieces were incubated in medium containing 10 mM nicotinamide. Although the incubation caused an elevation of cellular NAD+ levels and of glucose uptake from the medium to control values, it did not result in a substantial reduction of cell death or microblister formation as observed by light microscopy in tissue sections.