title: Histopathological changes in Yucatan minipig skin following challenge with sulphur mustard. A sequential study of the first 24 hours following challenge.
abstract: Sulphur mustard (HD) or "mustard gas' is a potent vesicant chemical warfare agent whose biological effects in man have been well documented. The histopathological features of the developing cutaneous HD lesion in female Yucatan minipigs up to 24 hours post exposure are reported. Following challenge with HD vapour at a concentration of 12.0 mumol/cm2 a sequence of ultrastructural changes to keratinocytes occurred which were initially seen in the stratum basale. Condensation of nuclear heterochromatin and loss of euchromatin was accompanied by cytoplasmic swelling and culminated in focal epidermal necrosis which was evident at 24 h after the challenge. The melanocyte appeared to be the cell type most sensitive to HD challenge with a loss of cytoplasmic electron density in areas of the cytoplasm immediately surrounding the melanosomes, chromatin condensation, nuclear membrane blebbing with mitochondrial and generalized cytoplasmic swelling. Isolated complete cell necrosis and disruption were noted as early as 2 h following the challenge with generalized necrosis being seen from 12 h onwards. From 12 h onwards, areas of basement membrane degeneration were also observed. These appeared similar in ultrastructure to that observed in other animal model systems but did not progress to the large blisters so typical of the human lesion. Damage to the upper dermis took the form of an inflammatory response typified by vascular endothelial swelling and vacuolation, dermal oedema and inflammatory cell (mainly neutrophil) infiltration. There was some evidence of transitory epidermal damage outside the prescribed wound area. This finding may be of clinical importance when surgical treatments are being considered.
authors.affiliation: Defence Evaluation and Research Agency, Porton Down, Salisbury, UK.
authors.forename: R F
authors.initials: RF
authors.lastname: Brown
authors.forename: P
authors.initials: P
authors.lastname: Rice
mesh_terms: D000818:Animals; D002619:Chemical Warfare Agents / Q000633:toxicity*; D005260:Female; D015603:Keratinocytes / Q000187:drug effects / Q000648:ultrastructure; D008544:Melanocytes / Q000187:drug effects / Q000648:ultrastructure; D008854:Microscopy, Electron; D009151:Mustard Gas / Q000633:toxicity*; D012867:Skin / Q000187:drug effects* / Q000648:ultrastructure*; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors
chemical_list: D002619:Chemical Warfare Agents; D009151:Mustard Gas