Comparison of the toxicity of sulfur mustard and its oxidation products in vitro
The molecular toxicology of the chemical warfare agent sulfur mustard (SM) is still not completely understood. It has been suggested that in addition to SM itself also biotransformation products thereof mediate cytotoxicity. In the current study, we assessed this aspect by exposing a human hepatocyt...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Tsoutsoulopoulos, Amelie [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2020transfer abstract |
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| Schlagwörter: |
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| Umfang: |
4 |
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| Übergeordnetes Werk: |
Enthalten in: Toxicology letters - Chen, Yun-Ru ELSEVIER, 2019, an international journal for the rapid publication of short reports on all aspects of toxicology especially mechanisms of toxicity, Amsterdam [u.a.] |
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| Übergeordnetes Werk: |
volume:321 ; year:2020 ; day:15 ; month:03 ; pages:69-72 ; extent:4 |
| Links: |
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| DOI / URN: |
10.1016/j.toxlet.2019.12.015 |
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ELV049049313 |
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| 520 | |a The molecular toxicology of the chemical warfare agent sulfur mustard (SM) is still not completely understood. It has been suggested that in addition to SM itself also biotransformation products thereof mediate cytotoxicity. In the current study, we assessed this aspect by exposing a human hepatocyte cell line (HepG2) to SM or to its oxidation products sulfur mustard sulfoxide (SMO), sulfur mustard sulfone (SMO2), and divinyl sulfone (DVS). Cytotoxicity, determined with the XTT assay, revealed a significant higher toxicity of SMO2 and DVS compared to SM while SMO had no effect at any concentration. The exact biotransformation of SM leading to SMO, SMO2 and finally DVS is unknown so far. Involvement of the CYP450 system is discussed and was also investigated in the presented study. Modulation of CYP1A2 activity, taken as a model enzyme for CYP450, affected cytotoxicity of SM, SMO2 or DVS significantly. Induction of CYP1A2 with omeprazole led to decreased cytotoxicity for all compounds whereas inhibition with cimetidine resulted in an increased cytotoxicity for SM, but not for SMO2 and DVS. Our results indicate a distinctive role of the CYP450 system in SM poisoning. Future studies should address the metabolic conversion of SM in more detail. Our data may suggest the well-tolerated drug omeprazole as a potential co-treatment after contact to SM. | ||
| 520 | |a The molecular toxicology of the chemical warfare agent sulfur mustard (SM) is still not completely understood. It has been suggested that in addition to SM itself also biotransformation products thereof mediate cytotoxicity. In the current study, we assessed this aspect by exposing a human hepatocyte cell line (HepG2) to SM or to its oxidation products sulfur mustard sulfoxide (SMO), sulfur mustard sulfone (SMO2), and divinyl sulfone (DVS). Cytotoxicity, determined with the XTT assay, revealed a significant higher toxicity of SMO2 and DVS compared to SM while SMO had no effect at any concentration. The exact biotransformation of SM leading to SMO, SMO2 and finally DVS is unknown so far. Involvement of the CYP450 system is discussed and was also investigated in the presented study. Modulation of CYP1A2 activity, taken as a model enzyme for CYP450, affected cytotoxicity of SM, SMO2 or DVS significantly. Induction of CYP1A2 with omeprazole led to decreased cytotoxicity for all compounds whereas inhibition with cimetidine resulted in an increased cytotoxicity for SM, but not for SMO2 and DVS. Our results indicate a distinctive role of the CYP450 system in SM poisoning. Future studies should address the metabolic conversion of SM in more detail. Our data may suggest the well-tolerated drug omeprazole as a potential co-treatment after contact to SM. | ||
| 650 | 7 | |a SM oxidation |2 Elsevier | |
| 650 | 7 | |a CYP1A2 |2 Elsevier | |
| 650 | 7 | |a HepG2 cells |2 Elsevier | |
| 650 | 7 | |a SMO, SMO2, DVS, cytotoxicity |2 Elsevier | |
| 700 | 1 | |a Brockmöller, Sabrina |4 oth | |
| 700 | 1 | |a Thiermann, Horst |4 oth | |
| 700 | 1 | |a Steinritz, Dirk |4 oth | |
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2020 |
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10.1016/j.toxlet.2019.12.015 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000000872.pica (DE-627)ELV049049313 (ELSEVIER)S0378-4274(19)30408-4 DE-627 ger DE-627 rakwb eng 610 VZ 42.13 bkl 44.33 bkl Tsoutsoulopoulos, Amelie verfasserin aut Comparison of the toxicity of sulfur mustard and its oxidation products in vitro 2020transfer abstract 4 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The molecular toxicology of the chemical warfare agent sulfur mustard (SM) is still not completely understood. It has been suggested that in addition to SM itself also biotransformation products thereof mediate cytotoxicity. In the current study, we assessed this aspect by exposing a human hepatocyte cell line (HepG2) to SM or to its oxidation products sulfur mustard sulfoxide (SMO), sulfur mustard sulfone (SMO2), and divinyl sulfone (DVS). Cytotoxicity, determined with the XTT assay, revealed a significant higher toxicity of SMO2 and DVS compared to SM while SMO had no effect at any concentration. The exact biotransformation of SM leading to SMO, SMO2 and finally DVS is unknown so far. Involvement of the CYP450 system is discussed and was also investigated in the presented study. Modulation of CYP1A2 activity, taken as a model enzyme for CYP450, affected cytotoxicity of SM, SMO2 or DVS significantly. Induction of CYP1A2 with omeprazole led to decreased cytotoxicity for all compounds whereas inhibition with cimetidine resulted in an increased cytotoxicity for SM, but not for SMO2 and DVS. Our results indicate a distinctive role of the CYP450 system in SM poisoning. Future studies should address the metabolic conversion of SM in more detail. Our data may suggest the well-tolerated drug omeprazole as a potential co-treatment after contact to SM. The molecular toxicology of the chemical warfare agent sulfur mustard (SM) is still not completely understood. It has been suggested that in addition to SM itself also biotransformation products thereof mediate cytotoxicity. In the current study, we assessed this aspect by exposing a human hepatocyte cell line (HepG2) to SM or to its oxidation products sulfur mustard sulfoxide (SMO), sulfur mustard sulfone (SMO2), and divinyl sulfone (DVS). Cytotoxicity, determined with the XTT assay, revealed a significant higher toxicity of SMO2 and DVS compared to SM while SMO had no effect at any concentration. The exact biotransformation of SM leading to SMO, SMO2 and finally DVS is unknown so far. Involvement of the CYP450 system is discussed and was also investigated in the presented study. Modulation of CYP1A2 activity, taken as a model enzyme for CYP450, affected cytotoxicity of SM, SMO2 or DVS significantly. Induction of CYP1A2 with omeprazole led to decreased cytotoxicity for all compounds whereas inhibition with cimetidine resulted in an increased cytotoxicity for SM, but not for SMO2 and DVS. Our results indicate a distinctive role of the CYP450 system in SM poisoning. Future studies should address the metabolic conversion of SM in more detail. Our data may suggest the well-tolerated drug omeprazole as a potential co-treatment after contact to SM. SM oxidation Elsevier CYP1A2 Elsevier HepG2 cells Elsevier SMO, SMO2, DVS, cytotoxicity Elsevier Brockmöller, Sabrina oth Thiermann, Horst oth Steinritz, Dirk oth Enthalten in Elsevier Science Chen, Yun-Ru ELSEVIER Toxicology letters 2019 an international journal for the rapid publication of short reports on all aspects of toxicology especially mechanisms of toxicity Amsterdam [u.a.] (DE-627)ELV003574431 volume:321 year:2020 day:15 month:03 pages:69-72 extent:4 https://doi.org/10.1016/j.toxlet.2019.12.015 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 42.13 Molekularbiologie VZ 44.33 Physiologische Chemie VZ AR 321 2020 15 0315 69-72 4 |
| spelling |
10.1016/j.toxlet.2019.12.015 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000000872.pica (DE-627)ELV049049313 (ELSEVIER)S0378-4274(19)30408-4 DE-627 ger DE-627 rakwb eng 610 VZ 42.13 bkl 44.33 bkl Tsoutsoulopoulos, Amelie verfasserin aut Comparison of the toxicity of sulfur mustard and its oxidation products in vitro 2020transfer abstract 4 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The molecular toxicology of the chemical warfare agent sulfur mustard (SM) is still not completely understood. It has been suggested that in addition to SM itself also biotransformation products thereof mediate cytotoxicity. In the current study, we assessed this aspect by exposing a human hepatocyte cell line (HepG2) to SM or to its oxidation products sulfur mustard sulfoxide (SMO), sulfur mustard sulfone (SMO2), and divinyl sulfone (DVS). Cytotoxicity, determined with the XTT assay, revealed a significant higher toxicity of SMO2 and DVS compared to SM while SMO had no effect at any concentration. The exact biotransformation of SM leading to SMO, SMO2 and finally DVS is unknown so far. Involvement of the CYP450 system is discussed and was also investigated in the presented study. Modulation of CYP1A2 activity, taken as a model enzyme for CYP450, affected cytotoxicity of SM, SMO2 or DVS significantly. Induction of CYP1A2 with omeprazole led to decreased cytotoxicity for all compounds whereas inhibition with cimetidine resulted in an increased cytotoxicity for SM, but not for SMO2 and DVS. Our results indicate a distinctive role of the CYP450 system in SM poisoning. Future studies should address the metabolic conversion of SM in more detail. Our data may suggest the well-tolerated drug omeprazole as a potential co-treatment after contact to SM. The molecular toxicology of the chemical warfare agent sulfur mustard (SM) is still not completely understood. It has been suggested that in addition to SM itself also biotransformation products thereof mediate cytotoxicity. In the current study, we assessed this aspect by exposing a human hepatocyte cell line (HepG2) to SM or to its oxidation products sulfur mustard sulfoxide (SMO), sulfur mustard sulfone (SMO2), and divinyl sulfone (DVS). Cytotoxicity, determined with the XTT assay, revealed a significant higher toxicity of SMO2 and DVS compared to SM while SMO had no effect at any concentration. The exact biotransformation of SM leading to SMO, SMO2 and finally DVS is unknown so far. Involvement of the CYP450 system is discussed and was also investigated in the presented study. Modulation of CYP1A2 activity, taken as a model enzyme for CYP450, affected cytotoxicity of SM, SMO2 or DVS significantly. Induction of CYP1A2 with omeprazole led to decreased cytotoxicity for all compounds whereas inhibition with cimetidine resulted in an increased cytotoxicity for SM, but not for SMO2 and DVS. Our results indicate a distinctive role of the CYP450 system in SM poisoning. Future studies should address the metabolic conversion of SM in more detail. Our data may suggest the well-tolerated drug omeprazole as a potential co-treatment after contact to SM. SM oxidation Elsevier CYP1A2 Elsevier HepG2 cells Elsevier SMO, SMO2, DVS, cytotoxicity Elsevier Brockmöller, Sabrina oth Thiermann, Horst oth Steinritz, Dirk oth Enthalten in Elsevier Science Chen, Yun-Ru ELSEVIER Toxicology letters 2019 an international journal for the rapid publication of short reports on all aspects of toxicology especially mechanisms of toxicity Amsterdam [u.a.] (DE-627)ELV003574431 volume:321 year:2020 day:15 month:03 pages:69-72 extent:4 https://doi.org/10.1016/j.toxlet.2019.12.015 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 42.13 Molekularbiologie VZ 44.33 Physiologische Chemie VZ AR 321 2020 15 0315 69-72 4 |
| allfields_unstemmed |
10.1016/j.toxlet.2019.12.015 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000000872.pica (DE-627)ELV049049313 (ELSEVIER)S0378-4274(19)30408-4 DE-627 ger DE-627 rakwb eng 610 VZ 42.13 bkl 44.33 bkl Tsoutsoulopoulos, Amelie verfasserin aut Comparison of the toxicity of sulfur mustard and its oxidation products in vitro 2020transfer abstract 4 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The molecular toxicology of the chemical warfare agent sulfur mustard (SM) is still not completely understood. It has been suggested that in addition to SM itself also biotransformation products thereof mediate cytotoxicity. In the current study, we assessed this aspect by exposing a human hepatocyte cell line (HepG2) to SM or to its oxidation products sulfur mustard sulfoxide (SMO), sulfur mustard sulfone (SMO2), and divinyl sulfone (DVS). Cytotoxicity, determined with the XTT assay, revealed a significant higher toxicity of SMO2 and DVS compared to SM while SMO had no effect at any concentration. The exact biotransformation of SM leading to SMO, SMO2 and finally DVS is unknown so far. Involvement of the CYP450 system is discussed and was also investigated in the presented study. Modulation of CYP1A2 activity, taken as a model enzyme for CYP450, affected cytotoxicity of SM, SMO2 or DVS significantly. Induction of CYP1A2 with omeprazole led to decreased cytotoxicity for all compounds whereas inhibition with cimetidine resulted in an increased cytotoxicity for SM, but not for SMO2 and DVS. Our results indicate a distinctive role of the CYP450 system in SM poisoning. Future studies should address the metabolic conversion of SM in more detail. Our data may suggest the well-tolerated drug omeprazole as a potential co-treatment after contact to SM. The molecular toxicology of the chemical warfare agent sulfur mustard (SM) is still not completely understood. It has been suggested that in addition to SM itself also biotransformation products thereof mediate cytotoxicity. In the current study, we assessed this aspect by exposing a human hepatocyte cell line (HepG2) to SM or to its oxidation products sulfur mustard sulfoxide (SMO), sulfur mustard sulfone (SMO2), and divinyl sulfone (DVS). Cytotoxicity, determined with the XTT assay, revealed a significant higher toxicity of SMO2 and DVS compared to SM while SMO had no effect at any concentration. The exact biotransformation of SM leading to SMO, SMO2 and finally DVS is unknown so far. Involvement of the CYP450 system is discussed and was also investigated in the presented study. Modulation of CYP1A2 activity, taken as a model enzyme for CYP450, affected cytotoxicity of SM, SMO2 or DVS significantly. Induction of CYP1A2 with omeprazole led to decreased cytotoxicity for all compounds whereas inhibition with cimetidine resulted in an increased cytotoxicity for SM, but not for SMO2 and DVS. Our results indicate a distinctive role of the CYP450 system in SM poisoning. Future studies should address the metabolic conversion of SM in more detail. Our data may suggest the well-tolerated drug omeprazole as a potential co-treatment after contact to SM. SM oxidation Elsevier CYP1A2 Elsevier HepG2 cells Elsevier SMO, SMO2, DVS, cytotoxicity Elsevier Brockmöller, Sabrina oth Thiermann, Horst oth Steinritz, Dirk oth Enthalten in Elsevier Science Chen, Yun-Ru ELSEVIER Toxicology letters 2019 an international journal for the rapid publication of short reports on all aspects of toxicology especially mechanisms of toxicity Amsterdam [u.a.] (DE-627)ELV003574431 volume:321 year:2020 day:15 month:03 pages:69-72 extent:4 https://doi.org/10.1016/j.toxlet.2019.12.015 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 42.13 Molekularbiologie VZ 44.33 Physiologische Chemie VZ AR 321 2020 15 0315 69-72 4 |
| allfieldsGer |
10.1016/j.toxlet.2019.12.015 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000000872.pica (DE-627)ELV049049313 (ELSEVIER)S0378-4274(19)30408-4 DE-627 ger DE-627 rakwb eng 610 VZ 42.13 bkl 44.33 bkl Tsoutsoulopoulos, Amelie verfasserin aut Comparison of the toxicity of sulfur mustard and its oxidation products in vitro 2020transfer abstract 4 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The molecular toxicology of the chemical warfare agent sulfur mustard (SM) is still not completely understood. It has been suggested that in addition to SM itself also biotransformation products thereof mediate cytotoxicity. In the current study, we assessed this aspect by exposing a human hepatocyte cell line (HepG2) to SM or to its oxidation products sulfur mustard sulfoxide (SMO), sulfur mustard sulfone (SMO2), and divinyl sulfone (DVS). Cytotoxicity, determined with the XTT assay, revealed a significant higher toxicity of SMO2 and DVS compared to SM while SMO had no effect at any concentration. The exact biotransformation of SM leading to SMO, SMO2 and finally DVS is unknown so far. Involvement of the CYP450 system is discussed and was also investigated in the presented study. Modulation of CYP1A2 activity, taken as a model enzyme for CYP450, affected cytotoxicity of SM, SMO2 or DVS significantly. Induction of CYP1A2 with omeprazole led to decreased cytotoxicity for all compounds whereas inhibition with cimetidine resulted in an increased cytotoxicity for SM, but not for SMO2 and DVS. Our results indicate a distinctive role of the CYP450 system in SM poisoning. Future studies should address the metabolic conversion of SM in more detail. Our data may suggest the well-tolerated drug omeprazole as a potential co-treatment after contact to SM. The molecular toxicology of the chemical warfare agent sulfur mustard (SM) is still not completely understood. It has been suggested that in addition to SM itself also biotransformation products thereof mediate cytotoxicity. In the current study, we assessed this aspect by exposing a human hepatocyte cell line (HepG2) to SM or to its oxidation products sulfur mustard sulfoxide (SMO), sulfur mustard sulfone (SMO2), and divinyl sulfone (DVS). Cytotoxicity, determined with the XTT assay, revealed a significant higher toxicity of SMO2 and DVS compared to SM while SMO had no effect at any concentration. The exact biotransformation of SM leading to SMO, SMO2 and finally DVS is unknown so far. Involvement of the CYP450 system is discussed and was also investigated in the presented study. Modulation of CYP1A2 activity, taken as a model enzyme for CYP450, affected cytotoxicity of SM, SMO2 or DVS significantly. Induction of CYP1A2 with omeprazole led to decreased cytotoxicity for all compounds whereas inhibition with cimetidine resulted in an increased cytotoxicity for SM, but not for SMO2 and DVS. Our results indicate a distinctive role of the CYP450 system in SM poisoning. Future studies should address the metabolic conversion of SM in more detail. Our data may suggest the well-tolerated drug omeprazole as a potential co-treatment after contact to SM. SM oxidation Elsevier CYP1A2 Elsevier HepG2 cells Elsevier SMO, SMO2, DVS, cytotoxicity Elsevier Brockmöller, Sabrina oth Thiermann, Horst oth Steinritz, Dirk oth Enthalten in Elsevier Science Chen, Yun-Ru ELSEVIER Toxicology letters 2019 an international journal for the rapid publication of short reports on all aspects of toxicology especially mechanisms of toxicity Amsterdam [u.a.] (DE-627)ELV003574431 volume:321 year:2020 day:15 month:03 pages:69-72 extent:4 https://doi.org/10.1016/j.toxlet.2019.12.015 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 42.13 Molekularbiologie VZ 44.33 Physiologische Chemie VZ AR 321 2020 15 0315 69-72 4 |
| allfieldsSound |
10.1016/j.toxlet.2019.12.015 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000000872.pica (DE-627)ELV049049313 (ELSEVIER)S0378-4274(19)30408-4 DE-627 ger DE-627 rakwb eng 610 VZ 42.13 bkl 44.33 bkl Tsoutsoulopoulos, Amelie verfasserin aut Comparison of the toxicity of sulfur mustard and its oxidation products in vitro 2020transfer abstract 4 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The molecular toxicology of the chemical warfare agent sulfur mustard (SM) is still not completely understood. It has been suggested that in addition to SM itself also biotransformation products thereof mediate cytotoxicity. In the current study, we assessed this aspect by exposing a human hepatocyte cell line (HepG2) to SM or to its oxidation products sulfur mustard sulfoxide (SMO), sulfur mustard sulfone (SMO2), and divinyl sulfone (DVS). Cytotoxicity, determined with the XTT assay, revealed a significant higher toxicity of SMO2 and DVS compared to SM while SMO had no effect at any concentration. The exact biotransformation of SM leading to SMO, SMO2 and finally DVS is unknown so far. Involvement of the CYP450 system is discussed and was also investigated in the presented study. Modulation of CYP1A2 activity, taken as a model enzyme for CYP450, affected cytotoxicity of SM, SMO2 or DVS significantly. Induction of CYP1A2 with omeprazole led to decreased cytotoxicity for all compounds whereas inhibition with cimetidine resulted in an increased cytotoxicity for SM, but not for SMO2 and DVS. Our results indicate a distinctive role of the CYP450 system in SM poisoning. Future studies should address the metabolic conversion of SM in more detail. Our data may suggest the well-tolerated drug omeprazole as a potential co-treatment after contact to SM. The molecular toxicology of the chemical warfare agent sulfur mustard (SM) is still not completely understood. It has been suggested that in addition to SM itself also biotransformation products thereof mediate cytotoxicity. In the current study, we assessed this aspect by exposing a human hepatocyte cell line (HepG2) to SM or to its oxidation products sulfur mustard sulfoxide (SMO), sulfur mustard sulfone (SMO2), and divinyl sulfone (DVS). Cytotoxicity, determined with the XTT assay, revealed a significant higher toxicity of SMO2 and DVS compared to SM while SMO had no effect at any concentration. The exact biotransformation of SM leading to SMO, SMO2 and finally DVS is unknown so far. Involvement of the CYP450 system is discussed and was also investigated in the presented study. Modulation of CYP1A2 activity, taken as a model enzyme for CYP450, affected cytotoxicity of SM, SMO2 or DVS significantly. Induction of CYP1A2 with omeprazole led to decreased cytotoxicity for all compounds whereas inhibition with cimetidine resulted in an increased cytotoxicity for SM, but not for SMO2 and DVS. Our results indicate a distinctive role of the CYP450 system in SM poisoning. Future studies should address the metabolic conversion of SM in more detail. Our data may suggest the well-tolerated drug omeprazole as a potential co-treatment after contact to SM. SM oxidation Elsevier CYP1A2 Elsevier HepG2 cells Elsevier SMO, SMO2, DVS, cytotoxicity Elsevier Brockmöller, Sabrina oth Thiermann, Horst oth Steinritz, Dirk oth Enthalten in Elsevier Science Chen, Yun-Ru ELSEVIER Toxicology letters 2019 an international journal for the rapid publication of short reports on all aspects of toxicology especially mechanisms of toxicity Amsterdam [u.a.] (DE-627)ELV003574431 volume:321 year:2020 day:15 month:03 pages:69-72 extent:4 https://doi.org/10.1016/j.toxlet.2019.12.015 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 42.13 Molekularbiologie VZ 44.33 Physiologische Chemie VZ AR 321 2020 15 0315 69-72 4 |
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Comparison of the toxicity of sulfur mustard and its oxidation products in vitro |
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The molecular toxicology of the chemical warfare agent sulfur mustard (SM) is still not completely understood. It has been suggested that in addition to SM itself also biotransformation products thereof mediate cytotoxicity. In the current study, we assessed this aspect by exposing a human hepatocyte cell line (HepG2) to SM or to its oxidation products sulfur mustard sulfoxide (SMO), sulfur mustard sulfone (SMO2), and divinyl sulfone (DVS). Cytotoxicity, determined with the XTT assay, revealed a significant higher toxicity of SMO2 and DVS compared to SM while SMO had no effect at any concentration. The exact biotransformation of SM leading to SMO, SMO2 and finally DVS is unknown so far. Involvement of the CYP450 system is discussed and was also investigated in the presented study. Modulation of CYP1A2 activity, taken as a model enzyme for CYP450, affected cytotoxicity of SM, SMO2 or DVS significantly. Induction of CYP1A2 with omeprazole led to decreased cytotoxicity for all compounds whereas inhibition with cimetidine resulted in an increased cytotoxicity for SM, but not for SMO2 and DVS. Our results indicate a distinctive role of the CYP450 system in SM poisoning. Future studies should address the metabolic conversion of SM in more detail. Our data may suggest the well-tolerated drug omeprazole as a potential co-treatment after contact to SM. |
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The molecular toxicology of the chemical warfare agent sulfur mustard (SM) is still not completely understood. It has been suggested that in addition to SM itself also biotransformation products thereof mediate cytotoxicity. In the current study, we assessed this aspect by exposing a human hepatocyte cell line (HepG2) to SM or to its oxidation products sulfur mustard sulfoxide (SMO), sulfur mustard sulfone (SMO2), and divinyl sulfone (DVS). Cytotoxicity, determined with the XTT assay, revealed a significant higher toxicity of SMO2 and DVS compared to SM while SMO had no effect at any concentration. The exact biotransformation of SM leading to SMO, SMO2 and finally DVS is unknown so far. Involvement of the CYP450 system is discussed and was also investigated in the presented study. Modulation of CYP1A2 activity, taken as a model enzyme for CYP450, affected cytotoxicity of SM, SMO2 or DVS significantly. Induction of CYP1A2 with omeprazole led to decreased cytotoxicity for all compounds whereas inhibition with cimetidine resulted in an increased cytotoxicity for SM, but not for SMO2 and DVS. Our results indicate a distinctive role of the CYP450 system in SM poisoning. Future studies should address the metabolic conversion of SM in more detail. Our data may suggest the well-tolerated drug omeprazole as a potential co-treatment after contact to SM. |
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The molecular toxicology of the chemical warfare agent sulfur mustard (SM) is still not completely understood. It has been suggested that in addition to SM itself also biotransformation products thereof mediate cytotoxicity. In the current study, we assessed this aspect by exposing a human hepatocyte cell line (HepG2) to SM or to its oxidation products sulfur mustard sulfoxide (SMO), sulfur mustard sulfone (SMO2), and divinyl sulfone (DVS). Cytotoxicity, determined with the XTT assay, revealed a significant higher toxicity of SMO2 and DVS compared to SM while SMO had no effect at any concentration. The exact biotransformation of SM leading to SMO, SMO2 and finally DVS is unknown so far. Involvement of the CYP450 system is discussed and was also investigated in the presented study. Modulation of CYP1A2 activity, taken as a model enzyme for CYP450, affected cytotoxicity of SM, SMO2 or DVS significantly. Induction of CYP1A2 with omeprazole led to decreased cytotoxicity for all compounds whereas inhibition with cimetidine resulted in an increased cytotoxicity for SM, but not for SMO2 and DVS. Our results indicate a distinctive role of the CYP450 system in SM poisoning. Future studies should address the metabolic conversion of SM in more detail. Our data may suggest the well-tolerated drug omeprazole as a potential co-treatment after contact to SM. |
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