HISTOPATHOLOGIC AND IMMUNOHISTOCHEMICAL FEATURES IN HUMAN SKIN AFTER EXPOSURE TO NITROGEN AND SULFUR MUSTARD

N-methyl-2,2'-dichlorodiethylamine (HN2) is a topical chemotherapeutic agent used as therapy for cutaneous T-cell lymphomas (CTCL). Di(2-chl oroethyl)sulfide (SM), and less often HN2, have been used as chemical weapons, with the skin being a principle target. The mechanisms by whi ch these chemicals produce their therapeutic and toxic effects in skin , however, are not clearly defined. We exposed human skin explants to two doses of HN2 and SM. At 18 hours after exposure, histopathologic f eatures were compared. in addition, immunohistochemical markers to bas ement membrane proteins were used to evaluate the effects of both chem icals on the basement membrane zone. Gross vesication was not seen. Py knotic nuclei with or without dyskeratotic changes within epidermal ke ratinocytes were present at both doses. These changes varied more betw een skin specimens than they did between doses. Ballooning degeneratio n was more marked after SM exposures. Diffuse dermal-epidermal separat ion was present only at high-dose exposures and did not appear to corr elate with the degree of changes locally in the overlying epidermis. A ntibodies to laminin-5 showed decreased immunoreactivity after exposur e to HN2 and SM. Immunoreactivity for laminin-was decreased to a lesse r extent, and immunoreactivity for collagen IV and VII was unchanged. HN2 and SM produce similar histopathologic and immunohistochemical fea tures after cutaneous exposure. These features suggest that part of me chanism of action of HN2 and SM is a direct effect on the basement mem brane zone. Understanding the effects of HN2 and SM separate from thei r effect on DNA may be important in designing therapies and in advanci ng our understanding of the pathophysiologic changes induced by these chemicals when delivered topically.