title: Time course of lesion development in the hairless guinea-pig model of sulfur mustard-induced dermal injury.
abstract: The objective of these studies was to provide detailed analyses of the time course of sulfur mustard (SM) vapor-induced clinical, histological, and biochemical changes following cutaneous exposure in hairless guinea-pigs. Three 6 cm(2) sites on the backs of each guinea-pig were exposed to SM vapor (314 mg(3) ) for 6 minutes (low dose) or 12 minutes (high dose). Animals were killed at 6, 24, and 48 hours, or 2 weeks postexposure. Erythema, edema, histopathology, and analysis of matrix metalloproteinase (MMP)-2 and -9 content were evaluated. Erythema was observed by 6 hours, and edema by 24 hours postexposure. Vapor exposure caused epidermal necrosis with varying degrees of dermatitis, ulceration, hemorrhage, and separation of the dermis from the epidermis. Later changes included epidermal regeneration with hyperplasia and formation of granulation tissue in the dermis with loss of hair follicles and glandular structures. Relative amounts of pro and active MMP-2 and MMP-9 were significantly increased in the high-dose SM group at 2 weeks. Erythema, edema, and histologic changes are consistent with findings among human victims of SM attack. This model, with observations to 2 weeks, will be useful in assessing the efficacy of countermeasures against SM.
authors.affiliation: CounterAct Research Center of Excellence, Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108, USA. jbenson@LRRI.org
authors.forename: Janet M
authors.initials: JM
authors.lastname: Benson
authors.forename: JeanClare
authors.initials: J
authors.lastname: Seagrave
authors.forename: Waylon M
authors.initials: WM
authors.lastname: Weber
authors.forename: Colleen D
authors.initials: CD
authors.lastname: Santistevan
authors.forename: Gary R
authors.initials: GR
authors.lastname: Grotendorst
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Schultz
authors.forename: Thomas H
authors.initials: TH
authors.lastname: March
mesh_terms: D000818:Animals; D002057:Burns, Chemical / Q000473:pathology; D003877:Dermatitis, Contact / Q000473:pathology*; D003879:Dermatologic Agents / Q000633:toxicity*; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced; D004890:Erythema / Q000139:chemically induced*; D006168:Guinea Pigs; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D009151:Mustard Gas / Q000633:toxicity*; D009336:Necrosis; D012867:Skin / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D013997:Time Factors; D014835:Volatilization
chemical_list: D003879:Dermatologic Agents; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D009151:Mustard Gas