title: Structural changes in hair follicles and sebaceous glands of hairless mice following exposure to sulfur mustard.
abstract: Sulfur mustard (SM) is a bifunctional alkylating agent causing skin inflammation, edema and blistering. A hallmark of SM-induced toxicity is follicular and interfollicular epithelial damage. In the present studies we determined if SM-induced structural alterations in hair follicles and sebaceous glands were correlated with cell damage, inflammation and wound healing. The dorsal skin of hairless mice was treated with saturated SM vapor. One to seven days later, epithelial cell karyolysis within the hair root sheath, infundibulum and isthmus was apparent, along with reduced numbers of sebocytes. Increased numbers of utriculi, some with connections to the skin surface, and engorged dermal cysts were also evident. This was associated with marked changes in expression of markers of DNA damage (phospho-H2A.X), apoptosis (cleaved caspase-3), and wound healing (FGFR2 and galectin-3) throughout pilosebaceous units. Conversely, fatty acid synthase and galectin-3 were down-regulated in sebocytes after SM. Decreased numbers of hair follicles and increased numbers of inflammatory cells surrounding the utriculi and follicular cysts were noted within the wound 3-7 days post-SM exposure. Expression of phospho-H2A.X, cleaved caspase-3, FGFR2 and galectin-3 was decreased in dysplastic follicular epidermis. Fourteen days after SM, engorged follicular cysts which expressed galectin-3 were noted within hyperplastic epidermis. Galectin-3 was also expressed in basal keratinocytes and in the first few layers of suprabasal keratinocytes in neoepidermis formed during wound healing indicating that this lectin is important in the early stages of keratinocyte differentiation. These data indicate that hair follicles and sebaceous glands are targets for SM in the skin.
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ, United States. Electronic address: lbjoseph@pharmacy.rutgers.edu.
authors.forename: Laurie B
authors.initials: LB
authors.lastname: Joseph
authors.affiliation: Environmental Health Science, New York Medical College, Valhalla, NY, United States.
authors.forename: Diane E
authors.initials: DE
authors.lastname: Heck
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ, United States.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Cervelli
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ, United States.
authors.forename: Gabriella M
authors.initials: GM
authors.lastname: Composto
authors.affiliation: Battelle Laboratories, Columbus, OH, United States.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Babin
authors.affiliation: MRIGlobal, Kansas City, MO, United States.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Casillas
authors.affiliation: Department of Pharmaceutics, Rutgers University, Piscataway, NJ, United States.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Sinko
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ, United States.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Gerecke
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ, United States.
authors.forename: Debra L
authors.initials: DL
authors.lastname: Laskin
authors.affiliation: Environmental and Occupational Medicine, Rutgers University - Robert Wood Johnson Medical School, Piscataway, NJ, United States.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Laskin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004195:Disease Models, Animal; D015536:Down-Regulation; D004847:Epithelial Cells / Q000187:drug effects; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism; D018859:Hair Follicle / Q000187:drug effects* / Q000473:pathology; D006657:Histones / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D009151:Mustard Gas / Q000633:toxicity*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism; D012627:Sebaceous Glands / Q000187:drug effects* / Q000473:pathology; D012867:Skin / Q000187:drug effects / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects
chemical_list: D053148:Caspase 3; D037502:Galectin 3; D006657:Histones; D009151:Mustard Gas; D051497:Receptor, Fibroblast Growth Factor, Type 2; C485095:Lgals3 protein, mouse; C496354:Fgfr2 protein, mouse; C505409:Casp3 protein, mouse; C475961:gamma-H2AX protein, mouse
keywords: Hair follicles; Phosphorylated histone H2A.X; Sebaceous glands; Sulfur mustard