Histopathologic and immunohistochemical features in human skin after exposure to nitrogen and sulfur mustard

Kathleen J. Smith, William J. Smith, Tracey Hamilton, Henry G. Skelton, John S. Graham, Carlin Okerberg, Robert Moeller, Brennie E. Hackley

Research output: Contribution to journalArticle

63 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)22-28
Number of pages7
JournalAmerican Journal of Dermatopathology
Volume20
Issue number1
DOIs
StatePublished - 1998
Externally publishedYes

Fingerprint

Mustard Gas
Mechlorethamine
Skin
Basement Membrane
Cutaneous T-Cell Lymphoma
Weapons
Poisons
Laminin
Therapeutic Uses
Blister
Keratinocytes
Epidermis
Membrane Proteins
Collagen
Antibodies
DNA
Therapeutics

Keywords

  • Chemical agents
  • Cutaneous histopathology
  • Nitrogen mustard
  • Sulfur mustard

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Dermatology

Cite this

Smith, K. J., Smith, W. J., Hamilton, T., Skelton, H. G., Graham, J. S., Okerberg, C., ... Hackley, B. E. (1998). Histopathologic and immunohistochemical features in human skin after exposure to nitrogen and sulfur mustard. American Journal of Dermatopathology, 20(1), 22-28. https://doi.org/10.1097/00000372-199802000-00005

Histopathologic and immunohistochemical features in human skin after exposure to nitrogen and sulfur mustard. / Smith, Kathleen J.; Smith, William J.; Hamilton, Tracey; Skelton, Henry G.; Graham, John S.; Okerberg, Carlin; Moeller, Robert; Hackley, Brennie E.

In: American Journal of Dermatopathology, Vol. 20, No. 1, 1998, p. 22-28.

Research output: Contribution to journalArticle

Smith, KJ, Smith, WJ, Hamilton, T, Skelton, HG, Graham, JS, Okerberg, C, Moeller, R & Hackley, BE 1998, 'Histopathologic and immunohistochemical features in human skin after exposure to nitrogen and sulfur mustard', American Journal of Dermatopathology, vol. 20, no. 1, pp. 22-28. https://doi.org/10.1097/00000372-199802000-00005
Smith, Kathleen J. ; Smith, William J. ; Hamilton, Tracey ; Skelton, Henry G. ; Graham, John S. ; Okerberg, Carlin ; Moeller, Robert ; Hackley, Brennie E. / Histopathologic and immunohistochemical features in human skin after exposure to nitrogen and sulfur mustard. In: American Journal of Dermatopathology. 1998 ; Vol. 20, No. 1. pp. 22-28.
@article{9d4b5bbc866c423da392b2abf8c0be1d,
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.",
keywords = "Chemical agents, Cutaneous histopathology, Nitrogen mustard, Sulfur mustard",
author = "Smith, {Kathleen J.} and Smith, {William J.} and Tracey Hamilton and Skelton, {Henry G.} and Graham, {John S.} and Carlin Okerberg and Robert Moeller and Hackley, {Brennie E.}",
year = "1998",
doi = "10.1097/00000372-199802000-00005",
language = "English (US)",
volume = "20",
pages = "22--28",
journal = "American Journal of Dermatopathology",
issn = "0193-1091",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Histopathologic and immunohistochemical features in human skin after exposure to nitrogen and sulfur mustard

AU - Smith, Kathleen J.

AU - Smith, William J.

AU - Hamilton, Tracey

AU - Skelton, Henry G.

AU - Graham, John S.

AU - Okerberg, Carlin

AU - Moeller, Robert

AU - Hackley, Brennie E.

PY - 1998

Y1 - 1998

N2 - 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.

AB - 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.

KW - Chemical agents

KW - Cutaneous histopathology

KW - Nitrogen mustard

KW - Sulfur mustard

UR - http://www.scopus.com/inward/record.url?scp=0031889026&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031889026&partnerID=8YFLogxK

U2 - 10.1097/00000372-199802000-00005

DO - 10.1097/00000372-199802000-00005

M3 - Article

C2 - 9504665

AN - SCOPUS:0031889026

VL - 20

SP - 22

EP - 28

JO - American Journal of Dermatopathology

JF - American Journal of Dermatopathology

SN - 0193-1091

IS - 1

ER -