title: Development of the sulfur mustard resistant keratinocyte cell line HaCaT/SM.
abstract: Pairs of corresponding cytotoxic drug sensitive and resistant cell lines are powerful tools to develop treatment strategies. Developing cytotoxic drug resistant cell lines is a well-established method in cancer research. In more than fifty years of sulfur mustard (SM) resistant research such a cell pair has never been produced. Hereinafter we describe the first successful approach to develop a SM resistant keratinocyte cell line. Starting with the SM sensitive keratinocyte cell line HaCaT we used a strategy of continuous exposure with gradually increased concentrations. Cells were cultured in total for more than 40 months starting with an initial concentration of 0.07μM SM twice a week up to a final concentration of 7.2μM SM. The achieved cell line HaCaT/SM had an LC50 resistance increase of 4.7-fold and an LC90 increase of 8.2-fold. Hereinafter we demonstrate the production of the first sulfur mustard (SM) resistant cell line. The new achieved cell line called HaCaT/SM is able to tolerate a continuous exposure of an SM concentration, which is associated with an inhibitory effect of 93% within the original HaCaT cells, which were used as starting point.
authors.affiliation: Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstraße 11, 80937 Munich, Germany; Department of Molecular and Cellular Sports Medicine, German Sports University, Am Sportpark Müngersdorf 6, 50933 Cologne, Germany. Electronic address: annette2schmidt@bundeswehr.org.
authors.forename: Annette
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstraße 11, 80937 Munich, Germany; Walther Straub Institute of Pharmacology and Toxicology, University of Munich, Goethestr. 33, 80336 Munich, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Steinritz
authors.affiliation: Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstraße 11, 80937 Munich, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Thiermann
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002619:Chemical Warfare Agents / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D006801:Humans; D020128:Inhibitory Concentration 50; D015603:Keratinocytes / Q000187:drug effects* / Q000473:pathology; D009151:Mustard Gas / Q000633:toxicity*; D013997:Time Factors
chemical_list: D002619:Chemical Warfare Agents; D009151:Mustard Gas
keywords: HaCaT/SM; Keratinocytes; Resistance; Sulfur mustard