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Horst Thiermann - One of the best experts on this subject based on the ideXlab platform.
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Cytostatic resistance profile of the sulfur mustard resistant Keratinocyte Cell Line HaCaT/SM.
Toxicology letters, 2018Co-Authors: Annette Schmidt, Dirk Steinritz, Markus Wolf, Simone Rothmiller, Franz Worek, Horst ThiermannAbstract:Abstract Background The Cell Line HaCaT/SM was developed as a sulfur mustard (SM) resistant Cell Line from the human Keratinocyte Cell Line HaCaT. This Cell Line was established to learn more about the effect of SM and possible therapeutic approaches to counteract the cytotoxic effects of SM. The aim of this study was to clarify whether the SM-resistant Cell Line HaCaT/SM exhibit also resistance to other alkylating agents or cytotoxic drugs with different mechanism of action. Material and method The chemosensitivity of SM-resistant human Keratinocyte Cell Line HaCaT/SM and the original Cell Line HaCaT were tested using the XTT assay. Nine cytotoxic drugs from five different substance groups were investigated. Results HaCaT/SM showed a significant increase in resistance against all tested drugs. From the substance class of the alkylating agents, HaCaT/SM showed the strongest resistance increase against chlorambucil (1.7 fold increase). Whereas over all substances strongest increase was observed against cisplatin (5.1 fold increase). Discussion The highest resistance was observed for cisplatin. The SM resistant Cells revealed changes in the miRNA profile as described before. The resistance to cisplatin is also connected to a specific miRNA profile. Interestingly, changes of miRNA-203 and miRNA-21 levels were found in HaCaT/SM as well as in cisplatin resistant Cells. It is therefore conceivable that the same resistance pathways are involved for both substances.
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Development of the sulfur mustard resistant Keratinocyte Cell Line HaCaT/SM
Toxicology letters, 2015Co-Authors: Annette M. Schmidt, Dirk Steinritz, Horst ThiermannAbstract: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.
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Characterization of sulfur mustard resistant Keratinocyte Cell Line HaCaT/SM
Toxicology letters, 2015Co-Authors: Markus Wolf, Dirk Steinritz, Horst Thiermann, Simone Rothmiller, Franz Worek, Markus Siegert, Nina Scheithauer, Romano Strobelt, Annette SchmidtAbstract:Abstract 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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Protective effects of the thiol compounds GSH and NAC against sulfur mustard toxicity in a human Keratinocyte Cell Line.
Toxicology letters, 2015Co-Authors: Frank Balszuweit, Horst Thiermann, Annette Schmidt, Franz Worek, Georg Menacher, Kai Kehe, Tanja Popp, Dirk SteinritzAbstract:Sulfur mustard (SM) is a chemical warfare agent causing blistering, inflammation and ulceration of the skin. Thiol compounds such as glutathione (GSH) and N-acetylcysteine (NAC) have been suggested as potential antidotes. We investigated SM toxicity in a human Keratinocyte Cell Line (HaCaT) and used GSH and NAC to counteract its cytotoxic effects. Cells were treated with 1, 5 or 10mM GSH or NAC and exposed to 30, 100 or 300μM SM. Different treatment regimens were applied to model extra- and intra-Cellular GSH/NAC effects on SM toxicity. Necrosis, apoptosis and interleukin-6 and -8 levels were determined 24h post-exposure. Necrosis and apoptosis increased with SM dose. Interleukin-6 and -8 production peaked at 100μM and decreased at 300μM probably due to reduced ability for interleukin biosynthesis. IntraCellular GSH/NAC diminished necrosis induced by 100μM SM. ExtraCellular GSH/NAC protected against necrosis and apoptosis induced by 100 and 300μM SM. Interleukin-6 and -8 production, induced by 100μM SM was reduced by GSH/NAC. However, low-dose GSH/NAC treatment of Cells exposed to 300μM SM led to increased interleukin production. Thus, moderately poisoned Cells are mostly responsible for SM-induced secretion of pro-inflammatory cytokines. GSH and NAC treatment can reduce SM-induced toxic effects. Protective effects were more pronounced by extraCellular GSH or NAC administration. Rescue of severely poisoned Cells may result in a strong secretion of pro- inflammatory cytokines. In summary, thiol compounds such as GSH or NAC constitute a promising approach to improve the therapy for SM injury. Additional intervention to prevent adverse effects of interleukin production might be beneficial.
Dirk Steinritz - One of the best experts on this subject based on the ideXlab platform.
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Cytostatic resistance profile of the sulfur mustard resistant Keratinocyte Cell Line HaCaT/SM.
Toxicology letters, 2018Co-Authors: Annette Schmidt, Dirk Steinritz, Markus Wolf, Simone Rothmiller, Franz Worek, Horst ThiermannAbstract:Abstract Background The Cell Line HaCaT/SM was developed as a sulfur mustard (SM) resistant Cell Line from the human Keratinocyte Cell Line HaCaT. This Cell Line was established to learn more about the effect of SM and possible therapeutic approaches to counteract the cytotoxic effects of SM. The aim of this study was to clarify whether the SM-resistant Cell Line HaCaT/SM exhibit also resistance to other alkylating agents or cytotoxic drugs with different mechanism of action. Material and method The chemosensitivity of SM-resistant human Keratinocyte Cell Line HaCaT/SM and the original Cell Line HaCaT were tested using the XTT assay. Nine cytotoxic drugs from five different substance groups were investigated. Results HaCaT/SM showed a significant increase in resistance against all tested drugs. From the substance class of the alkylating agents, HaCaT/SM showed the strongest resistance increase against chlorambucil (1.7 fold increase). Whereas over all substances strongest increase was observed against cisplatin (5.1 fold increase). Discussion The highest resistance was observed for cisplatin. The SM resistant Cells revealed changes in the miRNA profile as described before. The resistance to cisplatin is also connected to a specific miRNA profile. Interestingly, changes of miRNA-203 and miRNA-21 levels were found in HaCaT/SM as well as in cisplatin resistant Cells. It is therefore conceivable that the same resistance pathways are involved for both substances.
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Development of the sulfur mustard resistant Keratinocyte Cell Line HaCaT/SM
Toxicology letters, 2015Co-Authors: Annette M. Schmidt, Dirk Steinritz, Horst ThiermannAbstract: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.
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Characterization of sulfur mustard resistant Keratinocyte Cell Line HaCaT/SM
Toxicology letters, 2015Co-Authors: Markus Wolf, Dirk Steinritz, Horst Thiermann, Simone Rothmiller, Franz Worek, Markus Siegert, Nina Scheithauer, Romano Strobelt, Annette SchmidtAbstract:Abstract 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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Protective effects of the thiol compounds GSH and NAC against sulfur mustard toxicity in a human Keratinocyte Cell Line.
Toxicology letters, 2015Co-Authors: Frank Balszuweit, Horst Thiermann, Annette Schmidt, Franz Worek, Georg Menacher, Kai Kehe, Tanja Popp, Dirk SteinritzAbstract:Sulfur mustard (SM) is a chemical warfare agent causing blistering, inflammation and ulceration of the skin. Thiol compounds such as glutathione (GSH) and N-acetylcysteine (NAC) have been suggested as potential antidotes. We investigated SM toxicity in a human Keratinocyte Cell Line (HaCaT) and used GSH and NAC to counteract its cytotoxic effects. Cells were treated with 1, 5 or 10mM GSH or NAC and exposed to 30, 100 or 300μM SM. Different treatment regimens were applied to model extra- and intra-Cellular GSH/NAC effects on SM toxicity. Necrosis, apoptosis and interleukin-6 and -8 levels were determined 24h post-exposure. Necrosis and apoptosis increased with SM dose. Interleukin-6 and -8 production peaked at 100μM and decreased at 300μM probably due to reduced ability for interleukin biosynthesis. IntraCellular GSH/NAC diminished necrosis induced by 100μM SM. ExtraCellular GSH/NAC protected against necrosis and apoptosis induced by 100 and 300μM SM. Interleukin-6 and -8 production, induced by 100μM SM was reduced by GSH/NAC. However, low-dose GSH/NAC treatment of Cells exposed to 300μM SM led to increased interleukin production. Thus, moderately poisoned Cells are mostly responsible for SM-induced secretion of pro-inflammatory cytokines. GSH and NAC treatment can reduce SM-induced toxic effects. Protective effects were more pronounced by extraCellular GSH or NAC administration. Rescue of severely poisoned Cells may result in a strong secretion of pro- inflammatory cytokines. In summary, thiol compounds such as GSH or NAC constitute a promising approach to improve the therapy for SM injury. Additional intervention to prevent adverse effects of interleukin production might be beneficial.
Annette Schmidt - One of the best experts on this subject based on the ideXlab platform.
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Cytostatic resistance profile of the sulfur mustard resistant Keratinocyte Cell Line HaCaT/SM.
Toxicology letters, 2018Co-Authors: Annette Schmidt, Dirk Steinritz, Markus Wolf, Simone Rothmiller, Franz Worek, Horst ThiermannAbstract:Abstract Background The Cell Line HaCaT/SM was developed as a sulfur mustard (SM) resistant Cell Line from the human Keratinocyte Cell Line HaCaT. This Cell Line was established to learn more about the effect of SM and possible therapeutic approaches to counteract the cytotoxic effects of SM. The aim of this study was to clarify whether the SM-resistant Cell Line HaCaT/SM exhibit also resistance to other alkylating agents or cytotoxic drugs with different mechanism of action. Material and method The chemosensitivity of SM-resistant human Keratinocyte Cell Line HaCaT/SM and the original Cell Line HaCaT were tested using the XTT assay. Nine cytotoxic drugs from five different substance groups were investigated. Results HaCaT/SM showed a significant increase in resistance against all tested drugs. From the substance class of the alkylating agents, HaCaT/SM showed the strongest resistance increase against chlorambucil (1.7 fold increase). Whereas over all substances strongest increase was observed against cisplatin (5.1 fold increase). Discussion The highest resistance was observed for cisplatin. The SM resistant Cells revealed changes in the miRNA profile as described before. The resistance to cisplatin is also connected to a specific miRNA profile. Interestingly, changes of miRNA-203 and miRNA-21 levels were found in HaCaT/SM as well as in cisplatin resistant Cells. It is therefore conceivable that the same resistance pathways are involved for both substances.
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Characterization of sulfur mustard resistant Keratinocyte Cell Line HaCaT/SM
Toxicology letters, 2015Co-Authors: Markus Wolf, Dirk Steinritz, Horst Thiermann, Simone Rothmiller, Franz Worek, Markus Siegert, Nina Scheithauer, Romano Strobelt, Annette SchmidtAbstract:Abstract 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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Protective effects of the thiol compounds GSH and NAC against sulfur mustard toxicity in a human Keratinocyte Cell Line.
Toxicology letters, 2015Co-Authors: Frank Balszuweit, Horst Thiermann, Annette Schmidt, Franz Worek, Georg Menacher, Kai Kehe, Tanja Popp, Dirk SteinritzAbstract:Sulfur mustard (SM) is a chemical warfare agent causing blistering, inflammation and ulceration of the skin. Thiol compounds such as glutathione (GSH) and N-acetylcysteine (NAC) have been suggested as potential antidotes. We investigated SM toxicity in a human Keratinocyte Cell Line (HaCaT) and used GSH and NAC to counteract its cytotoxic effects. Cells were treated with 1, 5 or 10mM GSH or NAC and exposed to 30, 100 or 300μM SM. Different treatment regimens were applied to model extra- and intra-Cellular GSH/NAC effects on SM toxicity. Necrosis, apoptosis and interleukin-6 and -8 levels were determined 24h post-exposure. Necrosis and apoptosis increased with SM dose. Interleukin-6 and -8 production peaked at 100μM and decreased at 300μM probably due to reduced ability for interleukin biosynthesis. IntraCellular GSH/NAC diminished necrosis induced by 100μM SM. ExtraCellular GSH/NAC protected against necrosis and apoptosis induced by 100 and 300μM SM. Interleukin-6 and -8 production, induced by 100μM SM was reduced by GSH/NAC. However, low-dose GSH/NAC treatment of Cells exposed to 300μM SM led to increased interleukin production. Thus, moderately poisoned Cells are mostly responsible for SM-induced secretion of pro-inflammatory cytokines. GSH and NAC treatment can reduce SM-induced toxic effects. Protective effects were more pronounced by extraCellular GSH or NAC administration. Rescue of severely poisoned Cells may result in a strong secretion of pro- inflammatory cytokines. In summary, thiol compounds such as GSH or NAC constitute a promising approach to improve the therapy for SM injury. Additional intervention to prevent adverse effects of interleukin production might be beneficial.
Franz Worek - One of the best experts on this subject based on the ideXlab platform.
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Cytostatic resistance profile of the sulfur mustard resistant Keratinocyte Cell Line HaCaT/SM.
Toxicology letters, 2018Co-Authors: Annette Schmidt, Dirk Steinritz, Markus Wolf, Simone Rothmiller, Franz Worek, Horst ThiermannAbstract:Abstract Background The Cell Line HaCaT/SM was developed as a sulfur mustard (SM) resistant Cell Line from the human Keratinocyte Cell Line HaCaT. This Cell Line was established to learn more about the effect of SM and possible therapeutic approaches to counteract the cytotoxic effects of SM. The aim of this study was to clarify whether the SM-resistant Cell Line HaCaT/SM exhibit also resistance to other alkylating agents or cytotoxic drugs with different mechanism of action. Material and method The chemosensitivity of SM-resistant human Keratinocyte Cell Line HaCaT/SM and the original Cell Line HaCaT were tested using the XTT assay. Nine cytotoxic drugs from five different substance groups were investigated. Results HaCaT/SM showed a significant increase in resistance against all tested drugs. From the substance class of the alkylating agents, HaCaT/SM showed the strongest resistance increase against chlorambucil (1.7 fold increase). Whereas over all substances strongest increase was observed against cisplatin (5.1 fold increase). Discussion The highest resistance was observed for cisplatin. The SM resistant Cells revealed changes in the miRNA profile as described before. The resistance to cisplatin is also connected to a specific miRNA profile. Interestingly, changes of miRNA-203 and miRNA-21 levels were found in HaCaT/SM as well as in cisplatin resistant Cells. It is therefore conceivable that the same resistance pathways are involved for both substances.
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Characterization of sulfur mustard resistant Keratinocyte Cell Line HaCaT/SM
Toxicology letters, 2015Co-Authors: Markus Wolf, Dirk Steinritz, Horst Thiermann, Simone Rothmiller, Franz Worek, Markus Siegert, Nina Scheithauer, Romano Strobelt, Annette SchmidtAbstract:Abstract 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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Protective effects of the thiol compounds GSH and NAC against sulfur mustard toxicity in a human Keratinocyte Cell Line.
Toxicology letters, 2015Co-Authors: Frank Balszuweit, Horst Thiermann, Annette Schmidt, Franz Worek, Georg Menacher, Kai Kehe, Tanja Popp, Dirk SteinritzAbstract:Sulfur mustard (SM) is a chemical warfare agent causing blistering, inflammation and ulceration of the skin. Thiol compounds such as glutathione (GSH) and N-acetylcysteine (NAC) have been suggested as potential antidotes. We investigated SM toxicity in a human Keratinocyte Cell Line (HaCaT) and used GSH and NAC to counteract its cytotoxic effects. Cells were treated with 1, 5 or 10mM GSH or NAC and exposed to 30, 100 or 300μM SM. Different treatment regimens were applied to model extra- and intra-Cellular GSH/NAC effects on SM toxicity. Necrosis, apoptosis and interleukin-6 and -8 levels were determined 24h post-exposure. Necrosis and apoptosis increased with SM dose. Interleukin-6 and -8 production peaked at 100μM and decreased at 300μM probably due to reduced ability for interleukin biosynthesis. IntraCellular GSH/NAC diminished necrosis induced by 100μM SM. ExtraCellular GSH/NAC protected against necrosis and apoptosis induced by 100 and 300μM SM. Interleukin-6 and -8 production, induced by 100μM SM was reduced by GSH/NAC. However, low-dose GSH/NAC treatment of Cells exposed to 300μM SM led to increased interleukin production. Thus, moderately poisoned Cells are mostly responsible for SM-induced secretion of pro-inflammatory cytokines. GSH and NAC treatment can reduce SM-induced toxic effects. Protective effects were more pronounced by extraCellular GSH or NAC administration. Rescue of severely poisoned Cells may result in a strong secretion of pro- inflammatory cytokines. In summary, thiol compounds such as GSH or NAC constitute a promising approach to improve the therapy for SM injury. Additional intervention to prevent adverse effects of interleukin production might be beneficial.
Markus Wolf - One of the best experts on this subject based on the ideXlab platform.
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Cytostatic resistance profile of the sulfur mustard resistant Keratinocyte Cell Line HaCaT/SM.
Toxicology letters, 2018Co-Authors: Annette Schmidt, Dirk Steinritz, Markus Wolf, Simone Rothmiller, Franz Worek, Horst ThiermannAbstract:Abstract Background The Cell Line HaCaT/SM was developed as a sulfur mustard (SM) resistant Cell Line from the human Keratinocyte Cell Line HaCaT. This Cell Line was established to learn more about the effect of SM and possible therapeutic approaches to counteract the cytotoxic effects of SM. The aim of this study was to clarify whether the SM-resistant Cell Line HaCaT/SM exhibit also resistance to other alkylating agents or cytotoxic drugs with different mechanism of action. Material and method The chemosensitivity of SM-resistant human Keratinocyte Cell Line HaCaT/SM and the original Cell Line HaCaT were tested using the XTT assay. Nine cytotoxic drugs from five different substance groups were investigated. Results HaCaT/SM showed a significant increase in resistance against all tested drugs. From the substance class of the alkylating agents, HaCaT/SM showed the strongest resistance increase against chlorambucil (1.7 fold increase). Whereas over all substances strongest increase was observed against cisplatin (5.1 fold increase). Discussion The highest resistance was observed for cisplatin. The SM resistant Cells revealed changes in the miRNA profile as described before. The resistance to cisplatin is also connected to a specific miRNA profile. Interestingly, changes of miRNA-203 and miRNA-21 levels were found in HaCaT/SM as well as in cisplatin resistant Cells. It is therefore conceivable that the same resistance pathways are involved for both substances.
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Characterization of sulfur mustard resistant Keratinocyte Cell Line HaCaT/SM
Toxicology letters, 2015Co-Authors: Markus Wolf, Dirk Steinritz, Horst Thiermann, Simone Rothmiller, Franz Worek, Markus Siegert, Nina Scheithauer, Romano Strobelt, Annette SchmidtAbstract:Abstract 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.
