title: Histopathologic and immunohistochemical features in human skin after exposure to nitrogen and sulfur mustard.
abstract: N-methyl-2,2'-dichlorodiethylamine (HN2)is a topical chemotherapeutic agent used as therapy for cutaneous T-cell lymphomas (CTCL). Di(2-chloroethyl)sulfide (SM), and less often HN2, have been used as chemical weapons, with the skin being a principle target. The mechanisms by which 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 features were compared. In addition, immunohistochemical markers to basement membrane proteins were used to evaluate the effects of both chemicals on the basement membrane zone. Gross vesication was not seen. Pyknotic nuclei with or without dyskeratotic changes within epidermal keratinocytes were present at both doses. These changes varied more between skin specimens than they did between doses. Ballooning degeneration was more marked after SM exposures. Diffuse dermal-epidermal separation was present only at high-dose exposures and did not appear to correlate with the degree of changes locally in the overlying epidermis. Antibodies to laminin-5 showed decreased immunoreactivity after exposure to HN2 and SM. Immunoreactivity for laminin- was decreased to a lesser extent, and immunoreactivity for collagen IV and VII was unchanged. HN2 and SM produce similar histopathologic and immunohistochemical features after cutaneous exposure. These features suggest that part of mechanism of action of HN2 and SM is a direct effect on the basement membrane zone. Understanding the effects of HN2 and SM separate from their effect on DNA may be important in designing therapies and in advancing our understanding of the pathophysiologic changes induced by these chemicals when delivered topically.
authors.affiliation: United States Army Institute of Chemical Defense, Aberdeen, Maryland, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Smith
authors.forename: W J
authors.initials: WJ
authors.lastname: Smith
authors.forename: T
authors.initials: T
authors.lastname: Hamilton
authors.forename: H G
authors.initials: HG
authors.lastname: Skelton
authors.forename: J S
authors.initials: JS
authors.lastname: Graham
authors.forename: C
authors.initials: C
authors.lastname: Okerberg
authors.forename: R
authors.initials: R
authors.lastname: Moeller
authors.forename: B E
authors.initials: BE
authors.lastname: Hackley
mesh_terms: D001324:Autoantigens / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules / Q000032:analysis; D003094:Collagen / Q000032:analysis; D046508:Culture Techniques; D003598:Cytoskeletal Proteins; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000071821:Dystonin; D006801:Humans; D007150:Immunohistochemistry; D008466:Mechlorethamine / Q000008:administration & dosage / Q000009:adverse effects*; D009151:Mustard Gas / Q000008:administration & dosage / Q000009:adverse effects*; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D012867:Skin / Q000737:chemistry / Q000473:pathology*; D012871:Skin Diseases / Q000139:chemically induced* / Q000473:pathology; D000097794:Kalinin; D000097805:Collagen Type XVII
chemical_list: D001324:Autoantigens; D015415:Biomarkers; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D003094:Collagen; D003598:Cytoskeletal Proteins; D003879:Dermatologic Agents; D000071821:Dystonin; D008466:Mechlorethamine; D009151:Mustard Gas; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D000097794:Kalinin; D000097805:Collagen Type XVII; C486268:DST protein, human