Pathology Produced by Sulfur Mustard in Human Skin Grafts on Athymic Nude Mice. I. Gross and Light Microscopic Changes

Abstract

Sulfur mustard (SM) is a powerful vesicant in humans whose pathogenic mechanism is not well understood and an agent for which no effective therapy exists. We selected human skin grafted to congenitally athymic nude mice to study SM-induced injury because the injury in various animal models differs from skin injury in humans. Grafts made from full-thickness human neonatal foreskin or from partial-thickness adult facial, mammary, and abdominal skin were exposed to SM in either the liquid or vaporized form. The course of injury was followed at the gross, light microscopic, and ultrastructural levels. Morphologic changes were correlated to the dose. Changes occurring at the ultrastructural level are reported in a companion paper. Skin lesions in grafts had many features in common with those reported previously in humans including (a) similar dose-response for both liquid and vapor exposures; (b) similar time course for the appearance of overt pathology, preceded by a typical asymptomatic latent period of several hours; (c) similar cytotoxic action which is especially pronounced in basal cells of the epidermis and hair follicles and is characterized by pyknosis and edema followed by formation of large perinuclear and cytoplasmic vacuoles; (d) focal formation of similar microblisters which result from separation of the epidermis from the basement membrane; and (e) a similar inflammatory response which demonstrated dilatation of dermal blood vessels and infiltration of polymorphonuclear leukocytes into damaged epidermis. However, injury appeared to be less severe than that found in humans. There were no grossly visible bullae and there was an acceleration in healing time. Thus, the use of human skin grafted to nude mice offers a unique opportunity to study the effects of SM on human skin.