Inhibition of cytochrome P4501A by organotins in fish hepatoma cells PLHC-1
Inhibitory effects of several organotin compounds on cytochrome P4501A (CYP1A) induction response and enzyme activity have been analyzed in fish hepatoma cells (PLHC-1). In a first set of experiments, cells were exposed for 3 d to 3-methylcholanthrene (3-MC), an inducer of CYP1A. Simultaneously, ser...
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description | Inhibitory effects of several organotin compounds on cytochrome P4501A (CYP1A) induction response and enzyme activity have been analyzed in fish hepatoma cells (PLHC-1). In a first set of experiments, cells were exposed for 3 d to 3-methylcholanthrene (3-MC), an inducer of CYP1A. Simultaneously, series of dilutions of the widely used organotin compounds triphenyltin (TPT), tributyltin (TBT), dibutyltin (DBT), and monobutyltin (MBT) were added to the cells. Relative CYP1A protein contents were measured in an enzyme-linked immunosorbent assay (ELISA), CYP1A activities in the ethoxyresorufin-O-deethylase (EROD) assay, and cytotoxicity in the neutral red (NR) assay. Induction of CYP1A protein and activity was found in the presence of low concentrations of organotins and 3-MC. The three assays did not show significant differences in sensitivity for TBT and TPT. Concentrations that reduced control values by 50% (EC50) were between 1.6 X 10(-7) M and 3.5 X 10(-7) M, which emphasizes the high cytotoxicity of both compounds. In contrast, DBT led to inhibition of EROD activity at significantly lower concentrations (1.2 X 10(-6) M) than loss of CYP1A protein in the ELISA (9.0 X 10(-6) M) and cytotoxicity in the NR assay (8.7 X 10(-6) M). In a second set of experiments, reduction of CYP1A activity was also obtained after sequential exposure to 3-MC and organotins. In a third set of experiments, lysates of CYP1A-induced cells were exposed to organotins. Organotins caused a 50% inhibition of EROD activity at significantly higher concentrations (namely at 4.7 X 10(-5) M and 6.7 X 10(-5) M for TBT and DBT, respectively, and at 1.1 X 10(-3) M for MBT) than in the first set of experiments. For TBT, a noncompetitive inhibitory mechanism on CYP1A enzyme activity has been found. The experiments in this study demonstrate inhibitory capacities of TBT and TPT, but also of DBT and MBT, on the CYP1A system in fish cells |
doi_str_mv | 10.1002/etc.5620150518 |
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(EAWAG, Dubendorf, Switzerland.) ; Wurgler, F.E ; Fent, K</creator><creatorcontrib>Bruschweiler, B.J. (EAWAG, Dubendorf, Switzerland.) ; Wurgler, F.E ; Fent, K</creatorcontrib><description>Inhibitory effects of several organotin compounds on cytochrome P4501A (CYP1A) induction response and enzyme activity have been analyzed in fish hepatoma cells (PLHC-1). In a first set of experiments, cells were exposed for 3 d to 3-methylcholanthrene (3-MC), an inducer of CYP1A. Simultaneously, series of dilutions of the widely used organotin compounds triphenyltin (TPT), tributyltin (TBT), dibutyltin (DBT), and monobutyltin (MBT) were added to the cells. Relative CYP1A protein contents were measured in an enzyme-linked immunosorbent assay (ELISA), CYP1A activities in the ethoxyresorufin-O-deethylase (EROD) assay, and cytotoxicity in the neutral red (NR) assay. Induction of CYP1A protein and activity was found in the presence of low concentrations of organotins and 3-MC. The three assays did not show significant differences in sensitivity for TBT and TPT. Concentrations that reduced control values by 50% (EC50) were between 1.6 X 10(-7) M and 3.5 X 10(-7) M, which emphasizes the high cytotoxicity of both compounds. In contrast, DBT led to inhibition of EROD activity at significantly lower concentrations (1.2 X 10(-6) M) than loss of CYP1A protein in the ELISA (9.0 X 10(-6) M) and cytotoxicity in the NR assay (8.7 X 10(-6) M). In a second set of experiments, reduction of CYP1A activity was also obtained after sequential exposure to 3-MC and organotins. In a third set of experiments, lysates of CYP1A-induced cells were exposed to organotins. Organotins caused a 50% inhibition of EROD activity at significantly higher concentrations (namely at 4.7 X 10(-5) M and 6.7 X 10(-5) M for TBT and DBT, respectively, and at 1.1 X 10(-3) M for MBT) than in the first set of experiments. For TBT, a noncompetitive inhibitory mechanism on CYP1A enzyme activity has been found. The experiments in this study demonstrate inhibitory capacities of TBT and TPT, but also of DBT and MBT, on the CYP1A system in fish cells</description><identifier>ISSN: 0730-7268</identifier><identifier>EISSN: 1552-8618</identifier><identifier>DOI: 10.1002/etc.5620150518</identifier><identifier>CODEN: ETOCDK</identifier><language>eng</language><publisher>Hoboken: Wiley Periodicals, Inc</publisher><subject>ACTIVIDAD ENZIMATICA ; ACTIVITE ENZYMATIQUE ; Agnatha. Pisces ; Animal, plant and microbial ecology ; Applied ecology ; Biological and medical sciences ; CELLULE ; CELULAS ; CITOCROMO P 450 ; CITOCROMOS ; COMPOSE ORGANOSTANNIQUE ; COMPUESTO ORGANICO DEL ESTANO ; CONTAMINANTES ; CYP1A induction and inhibition ; CYTOCHROME ; CYTOCHROME P 450 ; Ecotoxicology, biological effects of pollution ; Effects of pollution and side effects of pesticides on vertebrates ; EXPERIMENTACION IN VITRO ; EXPERIMENTATION IN VITRO ; Fish hepatoma cells ; Freshwater ; Fundamental and applied biological sciences. Psychology ; INHIBICION ; INHIBITION ; NEOPLASMAS ; NEOPLASME ; Organotins ; Pisces ; POLLUANT ; TOXICIDAD ; TOXICITE</subject><ispartof>Environmental toxicology and chemistry, 1996-05, Vol.15 (5), p.728-735</ispartof><rights>Copyright © 1996 SETAC</rights><rights>1996 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4688-4d45cc55b83473d5fdc4b84c1633666d360ad4c5a697c8eb0af9b61261a5e5243</citedby><cites>FETCH-LOGICAL-c4688-4d45cc55b83473d5fdc4b84c1633666d360ad4c5a697c8eb0af9b61261a5e5243</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fetc.5620150518$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fetc.5620150518$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3089932$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>Bruschweiler, B.J. (EAWAG, Dubendorf, Switzerland.)</creatorcontrib><creatorcontrib>Wurgler, F.E</creatorcontrib><creatorcontrib>Fent, K</creatorcontrib><title>Inhibition of cytochrome P4501A by organotins in fish hepatoma cells PLHC-1</title><title>Environmental toxicology and chemistry</title><addtitle>Environmental Toxicology and Chemistry</addtitle><description>Inhibitory effects of several organotin compounds on cytochrome P4501A (CYP1A) induction response and enzyme activity have been analyzed in fish hepatoma cells (PLHC-1). In a first set of experiments, cells were exposed for 3 d to 3-methylcholanthrene (3-MC), an inducer of CYP1A. Simultaneously, series of dilutions of the widely used organotin compounds triphenyltin (TPT), tributyltin (TBT), dibutyltin (DBT), and monobutyltin (MBT) were added to the cells. Relative CYP1A protein contents were measured in an enzyme-linked immunosorbent assay (ELISA), CYP1A activities in the ethoxyresorufin-O-deethylase (EROD) assay, and cytotoxicity in the neutral red (NR) assay. Induction of CYP1A protein and activity was found in the presence of low concentrations of organotins and 3-MC. The three assays did not show significant differences in sensitivity for TBT and TPT. Concentrations that reduced control values by 50% (EC50) were between 1.6 X 10(-7) M and 3.5 X 10(-7) M, which emphasizes the high cytotoxicity of both compounds. In contrast, DBT led to inhibition of EROD activity at significantly lower concentrations (1.2 X 10(-6) M) than loss of CYP1A protein in the ELISA (9.0 X 10(-6) M) and cytotoxicity in the NR assay (8.7 X 10(-6) M). In a second set of experiments, reduction of CYP1A activity was also obtained after sequential exposure to 3-MC and organotins. In a third set of experiments, lysates of CYP1A-induced cells were exposed to organotins. Organotins caused a 50% inhibition of EROD activity at significantly higher concentrations (namely at 4.7 X 10(-5) M and 6.7 X 10(-5) M for TBT and DBT, respectively, and at 1.1 X 10(-3) M for MBT) than in the first set of experiments. For TBT, a noncompetitive inhibitory mechanism on CYP1A enzyme activity has been found. The experiments in this study demonstrate inhibitory capacities of TBT and TPT, but also of DBT and MBT, on the CYP1A system in fish cells</description><subject>ACTIVIDAD ENZIMATICA</subject><subject>ACTIVITE ENZYMATIQUE</subject><subject>Agnatha. Pisces</subject><subject>Animal, plant and microbial ecology</subject><subject>Applied ecology</subject><subject>Biological and medical sciences</subject><subject>CELLULE</subject><subject>CELULAS</subject><subject>CITOCROMO P 450</subject><subject>CITOCROMOS</subject><subject>COMPOSE ORGANOSTANNIQUE</subject><subject>COMPUESTO ORGANICO DEL ESTANO</subject><subject>CONTAMINANTES</subject><subject>CYP1A induction and inhibition</subject><subject>CYTOCHROME</subject><subject>CYTOCHROME P 450</subject><subject>Ecotoxicology, biological effects of pollution</subject><subject>Effects of pollution and side effects of pesticides on vertebrates</subject><subject>EXPERIMENTACION IN VITRO</subject><subject>EXPERIMENTATION IN VITRO</subject><subject>Fish hepatoma cells</subject><subject>Freshwater</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>INHIBICION</subject><subject>INHIBITION</subject><subject>NEOPLASMAS</subject><subject>NEOPLASME</subject><subject>Organotins</subject><subject>Pisces</subject><subject>POLLUANT</subject><subject>TOXICIDAD</subject><subject>TOXICITE</subject><issn>0730-7268</issn><issn>1552-8618</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><recordid>eNqFkU1vEzEQhi0EEqFw5cDJB8Rtg8cfs_axikhbEUElKEhcLK_X2xg269TeCvLv2WirIk45zeV5nxnNS8hrYEtgjL8Po18q5AwUU6CfkAUoxSuNoJ-SBasFq2qO-jl5UcpPxgCNMQvy8WrYxiaOMQ00ddQfxuS3Oe0CvZaKwTltDjTlWzekMQ6FxoF2sWzpNuzdmHaO-tD3hV5vLlcVvCTPOteX8OphnpGb9Yevq8tq8_nianW-qbxErSvZSuW9Uo0Wshat6lovGy09oBCI2ApkrpVeOTS116FhrjMNAkdwKiguxRl5N3v3Od3dhzLaXSzHQ9wQ0n2xgFxwJeA0KCU3UuBpUKAEqfgELmfQ51RKDp3d57hz-WCB2WMLdmrB_mthCrx9MLviXd9lN_hYHlOCaWPE0Wtm7Hfsw-GE1E7kfyuqORvLGP48Zl3-ZbEWtbLfP11Y822z1j_qtT2-783Mdy5Zd5unc26-GAQjlRF_AaoHrFc</recordid><startdate>199605</startdate><enddate>199605</enddate><creator>Bruschweiler, B.J. 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Pisces</topic><topic>Animal, plant and microbial ecology</topic><topic>Applied ecology</topic><topic>Biological and medical sciences</topic><topic>CELLULE</topic><topic>CELULAS</topic><topic>CITOCROMO P 450</topic><topic>CITOCROMOS</topic><topic>COMPOSE ORGANOSTANNIQUE</topic><topic>COMPUESTO ORGANICO DEL ESTANO</topic><topic>CONTAMINANTES</topic><topic>CYP1A induction and inhibition</topic><topic>CYTOCHROME</topic><topic>CYTOCHROME P 450</topic><topic>Ecotoxicology, biological effects of pollution</topic><topic>Effects of pollution and side effects of pesticides on vertebrates</topic><topic>EXPERIMENTACION IN VITRO</topic><topic>EXPERIMENTATION IN VITRO</topic><topic>Fish hepatoma cells</topic><topic>Freshwater</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>INHIBICION</topic><topic>INHIBITION</topic><topic>NEOPLASMAS</topic><topic>NEOPLASME</topic><topic>Organotins</topic><topic>Pisces</topic><topic>POLLUANT</topic><topic>TOXICIDAD</topic><topic>TOXICITE</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bruschweiler, B.J. (EAWAG, Dubendorf, Switzerland.)</creatorcontrib><creatorcontrib>Wurgler, F.E</creatorcontrib><creatorcontrib>Fent, K</creatorcontrib><collection>AGRIS</collection><collection>Istex</collection><collection>Pascal-Francis</collection><collection>CrossRef</collection><collection>Aqualine</collection><collection>Environment Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Environment Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Water Resources Abstracts</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><jtitle>Environmental toxicology and chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bruschweiler, B.J. (EAWAG, Dubendorf, Switzerland.)</au><au>Wurgler, F.E</au><au>Fent, K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of cytochrome P4501A by organotins in fish hepatoma cells PLHC-1</atitle><jtitle>Environmental toxicology and chemistry</jtitle><addtitle>Environmental Toxicology and Chemistry</addtitle><date>1996-05</date><risdate>1996</risdate><volume>15</volume><issue>5</issue><spage>728</spage><epage>735</epage><pages>728-735</pages><issn>0730-7268</issn><eissn>1552-8618</eissn><coden>ETOCDK</coden><abstract>Inhibitory effects of several organotin compounds on cytochrome P4501A (CYP1A) induction response and enzyme activity have been analyzed in fish hepatoma cells (PLHC-1). In a first set of experiments, cells were exposed for 3 d to 3-methylcholanthrene (3-MC), an inducer of CYP1A. Simultaneously, series of dilutions of the widely used organotin compounds triphenyltin (TPT), tributyltin (TBT), dibutyltin (DBT), and monobutyltin (MBT) were added to the cells. Relative CYP1A protein contents were measured in an enzyme-linked immunosorbent assay (ELISA), CYP1A activities in the ethoxyresorufin-O-deethylase (EROD) assay, and cytotoxicity in the neutral red (NR) assay. Induction of CYP1A protein and activity was found in the presence of low concentrations of organotins and 3-MC. The three assays did not show significant differences in sensitivity for TBT and TPT. Concentrations that reduced control values by 50% (EC50) were between 1.6 X 10(-7) M and 3.5 X 10(-7) M, which emphasizes the high cytotoxicity of both compounds. In contrast, DBT led to inhibition of EROD activity at significantly lower concentrations (1.2 X 10(-6) M) than loss of CYP1A protein in the ELISA (9.0 X 10(-6) M) and cytotoxicity in the NR assay (8.7 X 10(-6) M). In a second set of experiments, reduction of CYP1A activity was also obtained after sequential exposure to 3-MC and organotins. In a third set of experiments, lysates of CYP1A-induced cells were exposed to organotins. Organotins caused a 50% inhibition of EROD activity at significantly higher concentrations (namely at 4.7 X 10(-5) M and 6.7 X 10(-5) M for TBT and DBT, respectively, and at 1.1 X 10(-3) M for MBT) than in the first set of experiments. For TBT, a noncompetitive inhibitory mechanism on CYP1A enzyme activity has been found. The experiments in this study demonstrate inhibitory capacities of TBT and TPT, but also of DBT and MBT, on the CYP1A system in fish cells</abstract><cop>Hoboken</cop><pub>Wiley Periodicals, Inc</pub><doi>10.1002/etc.5620150518</doi><tpages>8</tpages></addata></record> |
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subjects | ACTIVIDAD ENZIMATICA ACTIVITE ENZYMATIQUE Agnatha. Pisces Animal, plant and microbial ecology Applied ecology Biological and medical sciences CELLULE CELULAS CITOCROMO P 450 CITOCROMOS COMPOSE ORGANOSTANNIQUE COMPUESTO ORGANICO DEL ESTANO CONTAMINANTES CYP1A induction and inhibition CYTOCHROME CYTOCHROME P 450 Ecotoxicology, biological effects of pollution Effects of pollution and side effects of pesticides on vertebrates EXPERIMENTACION IN VITRO EXPERIMENTATION IN VITRO Fish hepatoma cells Freshwater Fundamental and applied biological sciences. Psychology INHIBICION INHIBITION NEOPLASMAS NEOPLASME Organotins Pisces POLLUANT TOXICIDAD TOXICITE |
title | Inhibition of cytochrome P4501A by organotins in fish hepatoma cells PLHC-1 |
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