title: Tissue injury and repair following cutaneous exposure of mice to sulfur mustard.
abstract: In mouse skin, sulfur mustard (SM) is a potent vesicant, damaging both the epidermis and the dermis. The extent of wounding is dependent on the dose of SM and the duration of exposure. Initial responses include erythema, pruritus, edema, and xerosis; this is followed by an accumulation of inflammatory leukocytes in the tissue, activation of mast cells, and the release of mediators, including proinflammatory cytokines and bioactive lipids. These proinflammatory mediators contribute to damaging the epidermis, hair follicles, and sebaceous glands and to disruption of the epidermal basement membrane. This can lead to separation of the epidermis from the dermis, resulting in a blister, which ruptures, leading to the formation of an eschar. The eschar stimulates the formation of a neoepidermis and wound repair and may result in persistent epidermal hyperplasia. Epidermal damage and repair is associated with upregulation of enzymes generating proinflammatory and pro-growth/pro-wound healing mediators, including cyclooxygenase-2, which generates prostanoids, inducible nitric oxide synthase, which generates nitric oxide, fibroblast growth factor receptor 2, and galectin-3. Characterization of the mediators regulating structural changes in the skin during SM-induced tissue damage and wound healing will aid in the development of therapeutic modalities to mitigate toxicity and stimulate tissue repair processes.
authors.affiliation: Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey. lbjoseph@pharmacy.rutgers.edu.
authors.forename: Laurie B
authors.initials: LB
authors.lastname: Joseph
authors.affiliation: Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey.
authors.forename: Gabriella M
authors.initials: GM
authors.lastname: Composto
authors.affiliation: Department of Environmental Science, New York Medical College, Valhalla, New York.
authors.forename: Diane E
authors.initials: DE
authors.lastname: Heck
mesh_terms: D000818:Animals; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D009151:Mustard Gas / Q000008:administration & dosage / Q000633:toxicity*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D012871:Skin Diseases / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D018836:Inflammation Mediators; D009151:Mustard Gas
keywords: DNA damage; alkylating agents; skin; sulfur mustard; vesicants