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1.
Toxicol Lett ; 293: 62-66, 2018 Sep 01.
Article in English | MEDLINE | ID: mdl-29191789

ABSTRACT

The clinical progression following a sulfur mustard-induced skin exposure is well documented in the literature. Upon skin contact and a characteristic latency period, sulfur mustard (SM) causes erythema, blister formation and ulceration, which is associated with wound healing disorders that may require surgical treatment. Here, we present a case report of accidental exposure to SM in a laboratory setting which required surgical treatment of the skin. The case was illustrated at close intervals over a period of two years and underlines that exposure to SM has to be taken into account when typical clinical symptoms occur. Moreover skin grafts appear to be effective in SM-induced non healing skin ulcerations.


Subject(s)
Chemical Warfare Agents/poisoning , Mustard Gas/poisoning , Accidents , Adult , Blister/pathology , Erythema/pathology , Humans , Male , Occupational Exposure , Skin/pathology , Skin Transplantation/methods , Skin Ulcer/chemically induced , Skin Ulcer/pathology , Skin Ulcer/surgery
2.
Toxicol Lett ; 244: 95-102, 2016 Feb 26.
Article in English | MEDLINE | ID: mdl-26392148

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.


Subject(s)
Chemical Warfare Agents/toxicity , DNA Methylation/drug effects , Endothelial Cells/drug effects , Epigenesis, Genetic/drug effects , Mustard Gas/toxicity , Skin/drug effects , 5-Methylcytosine/metabolism , Animals , Cells, Cultured , Dose-Response Relationship, Drug , Endothelial Cells/metabolism , Endothelial Cells/pathology , Gene Expression Regulation , Histones/metabolism , Humans , Male , Mice , Protein Processing, Post-Translational/drug effects , Skin/metabolism , Skin/pathology , Time Factors
3.
Toxicol Lett ; 244: 112-120, 2016 Feb 26.
Article in English | MEDLINE | ID: mdl-26321678

ABSTRACT

Sulfur mustard (SM) is a chemical warfare agent (CWA) that was first used in World War I and in several military conflicts afterwards. The threat by SM is still present even today due to remaining stockpiles, old and abandoned remainders all over the world as well as to its ease of synthesis. CWA are banned by the Chemical Weapons Convention (CWC) interdicting their development, production, transport, stockpiling and use and are subjected to controlled destruction. The present case report describes an accidental exposure of three workers that occurred during the destruction of SM. All exposed workers presented a characteristic SM-related clinical picture that started about 4h after exposure with erythema and feeling of tension of the skin at the upper part of the body. Later on, superficial blister and a burning phenomenon of the affected skin areas developed. Similar symptoms occurred in all three patients differing severity. One patient presented sustained skin affections at the gluteal region while another patient came up with affections of the axilla and genital region. Fortunately, full recovery was observed on day 56 after exposure except some little pigmentation changes that were evident even on day 154 in two of the patients. SM-exposure was verified for all three patients using bioanalytical GC MS and LC MS/MS based methods applied to urine and plasma. Urinary biotransformation products of the ß-lyase pathway were detected until 5 days after poisoning whereas albumin-SM adducts could be found until day 29 underlining the beneficial role of adduct detection for post-exposure verification. In addition, we provide general recommendations for management and therapy in case of SM poisoning.


Subject(s)
Accidents , Blister/chemically induced , Chemical Warfare Agents/poisoning , Documentation , Erythema/chemically induced , Irritants/poisoning , Mustard Gas/poisoning , Skin/drug effects , Adult , Blister/diagnosis , Blister/therapy , Chemical Warfare Agents/metabolism , Chromatography, Liquid , Erythema/diagnosis , Erythema/therapy , Gas Chromatography-Mass Spectrometry , Humans , Male , Middle Aged , Mustard Gas/metabolism , Poisoning/diagnosis , Poisoning/therapy , Protein Binding , Remission Induction , Serum Albumin/metabolism , Serum Albumin, Human , Severity of Illness Index , Skin/pathology , Tandem Mass Spectrometry , Time Factors , Treatment Outcome
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