title: Epigenetic modulations in early endothelial cells and DNA hypermethylation in human skin after sulfur mustard exposure.
abstract: Victims that were exposed to the chemical warfare agent sulfur mustard (SM) suffer from chronic dermal and ocular lesions, severe pulmonary problems and cancer development. It has been proposed that epigenetic perturbations might be involved in that process but this has not been investigated so far. In this study, we investigated epigenetic modulations in vitro using early endothelial cells (EEC) that were exposed to different SM concentrations (0.5, 1.0, 23.5 and 50μM). A comprehensive analysis of 78 genes related to epigenetic pathways (i.e., DNA-methylation and post-translational histone modifications) was performed. Moreover, we analyzed global DNA methylation in vitro in EEC after SM exposure as a maker for epigenetic modulations and in vivo using human skin samples that were obtained from a patient 1 year after an accidently exposure to pure SM. SM exposure resulted in a complex regulation pattern of epigenetic modulators which was accompanied by a global increase of DNA methylation in vitro. Examination of the SM exposed human skin samples also revealed a significant increase of global DNA methylation in vivo, underlining the biological relevance of our findings. Thus, we demonstrated for the first time that SM affects epigenetic pathways and causes epigenetic modulations both in vivo and in vitro.
authors.affiliation: Bundeswehr Institute of Pharmacology and Toxicology, 80937 Munich, Germany; Walther-Straub-Institute of Pharmacology and Toxicology, Ludwig-Maximilians Universität München, 80336 Munich, Germany. Electronic address: dirk.steinritz@lrz.uni-muenchen.de.
authors.forename: Dirk
authors.initials: D
authors.lastname: Steinritz
authors.affiliation: Bundeswehr Institute of Pharmacology and Toxicology, 80937 Munich, Germany; Department of Molecular and Cellular Sports Medicine, German Sports University, 50933 Cologne, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Bundeswehr Institute of Pharmacology and Toxicology, 80937 Munich, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Balszuweit
authors.affiliation: Bundeswehr Institute of Pharmacology and Toxicology, 80937 Munich, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Thiermann
authors.affiliation: Bundeswehr Institute of Pharmacology and Toxicology, 80937 Munich, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: Simons
authors.affiliation: Department of Handsurgery, Plastic and Microsurgery, Burn Center, BG Trauma Hospital Hamburg, 21033 Hamburg, Germany.
authors.forename: Enno
authors.initials: E
authors.lastname: Striepling
authors.affiliation: Department of Molecular and Cellular Sports Medicine, German Sports University, 50933 Cologne, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Bölck
authors.affiliation: Department of Molecular and Cellular Sports Medicine, German Sports University, 50933 Cologne, Germany.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bloch
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002619:Chemical Warfare Agents / Q000633:toxicity*; D019175:DNA Methylation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D009151:Mustard Gas / Q000633:toxicity*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D002619:Chemical Warfare Agents; D006657:Histones; D044503:5-Methylcytosine; D009151:Mustard Gas
keywords: DNA methylation; Endothelial cells; Epigenetics; Human exposure; Sulfur mustard