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 language | English (US) |
|---|---|
| Pages (from-to) | 22-28 |
| Number of pages | 7 |
| Journal | American Journal of Dermatopathology |
| Volume | 20 |
| Issue number | 1 |
| DOIs | |
| State | Published - 1998 |
| Externally published | Yes |
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Keywords
- Chemical agents
- Cutaneous histopathology
- Nitrogen mustard
- Sulfur mustard
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Dermatology
Cite this
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 journal › Article
}
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 -