Pathogenesis of skin lesions caused by sulfur mustard

Robert F. Vogt, Arthur M. Dannenberg, Brian H. Schofield, Noreen A. Hynes, Bruno Papirmeister

Research output: Contribution to journalArticle

Abstract

Pathogenesis of Skin Lesions Caused by Sulfur Mustard. VOGT, R. F., JR., DANNENBERG, A. M., JR., SCHOFIELD, B. H., HYNES, N. A., AND PAPIRMEISTER, B. (1984). Fundam. Appl. Toxicol. 4, S71-S83. Sulfur mustard (SM) (di-2-chloroethyl sulfide), used for chemical warfare in World War I, is a highly reactive radiomimetic alkylating agent. When applied to the skin of rabbits and Guinea pigs, it produced vascular leakage, leukocyte infiltration, and slow death of basal epidermal cells. Thirty to sixty minutes after exposure to SM, injury to the superficial microvasculature (beneath the SM application site) was detected by measuring vascular leakage with Evans blue dye and also with horseradish peroxidase. At this same time, injury to the superficial fibroblasts was observed ultrastructurally; and an unexpectedly high percentage of basophils was found among the early infiltrating granulocytes. At 2 to 4 hr, the vascular leakage ceased, and had resumed by 8 hr in a more diffuse form. At this time, the basal epidermal cells showed pyknotic nuclei, an increase in their lysosomal enzymes (observed histochemically), and autophagic vacuoles (observed ultrastructurally). Leukocyte infiltration was marked, consisting mostly of heterophils (PMN) with a reduced percentage of basophils. During the next 24 to 72 hr, the entire inflammatory reaction reached its peak; and a superficial, crust-covered ulcer developed. Then, over the next 10 days, the lesion gradually subsided with concomitant repair and healing. Glucocorticosteroids decreased the early edematous phase, but did not affect the rate of healing. These findings suggest that the skin response to sulfur mustard has an immediate and a delayed phase. The immediate phase, I.e., within the first hour, was characterized by injury to the superficial fibroblasts and to the endothelium of superficial capillaries and venules, possibly because of direct damage to their cell membranes. At this time, a restricted vascular leakage and a selective granulocyte infiltration containing many basophils occurred. The delayed phase, which became evident after 8 hr, was characterized by the death of basal epidermal cells, probably because of DNA damage. This phase was accompanied by generalized vascular leakage, by massive heterophil immigration, and eventually by ulceration.

Original languageEnglish (US)
Pages (from-to)71-83
Number of pages13
JournalToxicological Sciences
Volume4
Issue number2 PART2
StatePublished - Apr 1984

Fingerprint

Mustard Gas
Skin
Blood Vessels
Basophils
Infiltration
Fibroblasts
Granulocytes
Wounds and Injuries
Leukocytes
Chemical Warfare
Cells
Chemical warfare
World War I
Evans Blue
Venules
Alkylating Agents
Emigration and Immigration
Vascular Endothelium
Horseradish Peroxidase
Cell membranes

ASJC Scopus subject areas

  • Molecular Biology
  • Embryology
  • Cell Biology
  • Genetics
  • Developmental Biology
  • Toxicology

Cite this

Vogt, R. F., Dannenberg, A. M., Schofield, B. H., Hynes, N. A., & Papirmeister, B. (1984). Pathogenesis of skin lesions caused by sulfur mustard. Toxicological Sciences, 4(2 PART2), 71-83.

Pathogenesis of skin lesions caused by sulfur mustard. / Vogt, Robert F.; Dannenberg, Arthur M.; Schofield, Brian H.; Hynes, Noreen A.; Papirmeister, Bruno.

In: Toxicological Sciences, Vol. 4, No. 2 PART2, 04.1984, p. 71-83.

Research output: Contribution to journalArticle

Vogt, RF, Dannenberg, AM, Schofield, BH, Hynes, NA & Papirmeister, B 1984, 'Pathogenesis of skin lesions caused by sulfur mustard', Toxicological Sciences, vol. 4, no. 2 PART2, pp. 71-83.
Vogt RF, Dannenberg AM, Schofield BH, Hynes NA, Papirmeister B. Pathogenesis of skin lesions caused by sulfur mustard. Toxicological Sciences. 1984 Apr;4(2 PART2):71-83.
Vogt, Robert F. ; Dannenberg, Arthur M. ; Schofield, Brian H. ; Hynes, Noreen A. ; Papirmeister, Bruno. / Pathogenesis of skin lesions caused by sulfur mustard. In: Toxicological Sciences. 1984 ; Vol. 4, No. 2 PART2. pp. 71-83.
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