Histologic Changes in Nude Mouse Skin and Human Skin Xenografts Following Exposure to Sulfhydryl Reagents: Arsenicals

Abstract

This report documents the histological changes in nude mouse skin and in human skin xenografts on nude mice following exposure to phenyldichloroarsine (PDA), a vesicant arsenical. Under light microscopy, we observed in PDA-treated human skin grafts: 1) degeneration of epidermal cell nuclei (apparent by 2 hr after exposure with increasing severity through 48 hr); 2) loss of epidermal cytoplasmic basophilia (apparent by 4 hr, maximal within 12 hr); 3) epidermal cytoplasmic vacuolization (vacuoles appeared within 4 hr and increased in size through 24 hr); 4) cleft formation within the basement membrane zone (apparent by 12 hr, increasing in severity through 24 hr); 5) inflammation evidenced by polymorphonuclear leukocyte (PMN) infiltration (apparent by 4 hr and increasing through 48 hr). The PMNs frequently formed a wall around the lesion, but did not infiltrate the treated area. Nude mouse skin reacted faster to PDA than did the grafts, but the histological changes were similar. Nude mouse hair follicles and sebaceous glands showed similar cellular changes at approximately the same time as did epidermal cells. Transmission electron microscopy of mouse skin exposed to PDA revealed a widening of intercellular spaces with attenuation of desmosomes. The subepidermal clefts resulted from separation within the lamina lucida with the lamina densa forming the base of the cleft. Diphenylchloroarsine caused lesions histologically indistinguishable from those of PDA. Lesions resulting from exposure to other sulfhydryl-binding compounds were very different from arsenical lesions. The arsenical-sensitive cellular constituents were not identified.