title: Temporal and spatial features of the formation of DNA adducts in sulfur mustard-exposed skin.
abstract: Sulfur mustard (SM) is a chemical warfare agent that targets skin where it induces large blisters. DNA alkylation is a critical step to explain SM-induced cutaneous symptoms. We determined the kinetics of formation of main SM-DNA adducts and compare it with the development of the SM-induced pathogenesis in skin. SKH-1 mice were exposed to 2, 6 and 60 mg/kg of SM and treated skin was biopsied between 6h and 21 days. Formation of SM DNA adducts was dose-dependent with a maximum immediately after exposure. However, adducts were persistent and still detectable 21 days post-exposure. The time-dependent formation of DNA adducts was also found to be correlated with the appearance of apoptotic cells. This temporal correlation suggests that these two early events are responsible for the severity of the damage to the skin. Besides, SM-DNA adducts were also detected in areas located next to contaminated zone, thus suggesting that SM diffuses in skin. Altogether, this work provides for the first time a clear picture of SM-induced genotoxicity using DNA adducts as a marker.
authors.affiliation: Laboratoire «Lésions des Acides Nucléiques», Université Joseph Fourier - Grenoble 1, CEA/Institut Nanoscience et Cryogénie/SCIB, UMR-E3, Grenoble, France; Département de Toxicologie et Risques Chimiques, Unité de Brûlure Chimique, Institut de Recherche Biomédicale des Armées, Antenne de La Tronche, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Batal
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boudry
authors.forename: Stéphane
authors.initials: S
authors.lastname: Mouret
authors.forename: Julien
authors.initials: J
authors.lastname: Wartelle
authors.forename: Sandy
authors.initials: S
authors.lastname: Emorine
authors.forename: Marine
authors.initials: M
authors.lastname: Bertoni
authors.forename: Izabel
authors.initials: I
authors.lastname: Bérard
authors.forename: Cécile
authors.initials: C
authors.lastname: Cléry-Barraud
authors.forename: Thierry
authors.initials: T
authors.lastname: Douki
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002619:Chemical Warfare Agents / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000187:drug effects* / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D008297:Male; D051379:Mice; D009151:Mustard Gas / Q000633:toxicity*; D012867:Skin / Q000187:drug effects* / Q000473:pathology
chemical_list: D002619:Chemical Warfare Agents; D018736:DNA Adducts; D009151:Mustard Gas
keywords: Apoptosis; DNA damage; DNA repair; Mass spectrometry; Skin; Sulfur mustard