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Characterization of sulfur mustard resistant keratinocyte cell line HaCaT/SM

TitleCharacterization of sulfur mustard resistant keratinocyte cell line HaCaT/SM
Publication TypeJournal Article
Year of Publication2015
AuthorsWolf M., Siegert M., Rothmiller S., Scheithauer N., Strobelt R., Steinritz D., Worek F., Thiermann H., Schmidt A.
JournalToxicol Lett
Date PublishedFeb 26
ISBN Number1879-3169 (Electronic)0378-4274 (Linking)
Keywords*Drug Resistance, Biomarkers/metabolism, Cell Line, Cell Nucleus/drug effects/metabolism/pathology, Cell Proliferation/drug effects, Cell Survival/drug effects, Chemical Warfare Agents/*toxicity, Cytokines/metabolism, DNA Adducts/metabolism, Dose-Response Relationship, Drug, Humans, Inhibitory Concentration 50, KERATINOCYTES, Keratinocytes/*drug effects/metabolism/pathology, Mustard Gas/*toxicity, Phenotype, RESISTANCE, Sulfur Mustard, Time Factors

BACKGROUND: The cell line HaCaT/SM was derived from the human keratinocyte cell line HaCaT. HaCaT/SM cells display a high resistance against sulfur mustard (SM). Intention of the presented study was to determine the cellular and molecular differences between HaCaT/SM and HaCaT so as to evaluate which changes might be responsible for being resistant against SM. METHODS: Both cell lines HaCaT and HaCaT/SM were analyzed with respect to their cell growth, nuclei perimeter, clonogenicity and secretion profile. Moreover DNA alkylation pattern under presence of SM was investigated. RESULTS: In comparison to HaCaT, the HaCaT/SM showed a significant smaller nuclei perimeter. For DNA alkylation a significant difference was observed over time. The clonogenicity of HaCaT/SM was increased to 150%. The secretion profile of these cells demonstrated a strong increase of ANG, PDGF-AA, TIMP1, TIMP2, and a decrease of AREG, CCL5, CXC1, CXC2/3, CXCL6, CXCL7, CXCL8, CXCL10, MIF, Trappin-1. CONCLUSION: The sulfur mustard (SM) resistant cell line HaCaT/SM demonstrates a wide range of significant differences to their origin cell line HaCaT. These differences might be responsible to provide resistance against SM and might also be useful to establish treatment concepts for humans after SM exposure.


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