Musk ketone enhances benzo(a)pyrene induced mutagenicity in human derived Hep G2 cells
Identifieur interne : 001505 ( Istex/Corpus ); précédent : 001504; suivant : 001506Musk ketone enhances benzo(a)pyrene induced mutagenicity in human derived Hep G2 cells
Auteurs : Volker Mersch-Sundermann ; Heidi Schneider ; Christian Freywald ; Cornelia Jenter ; Wolfram Parzefall ; Siegfried KnasmüllerSource :
- Mutation Research - Genetic Toxicology and Environmental Mutagenesis [ 1383-5718 ] ; 2001.
English descriptors
- KwdEn :
- AC, Arochlor 1254, B(a)P, benzo(a)pyrene, BNC, binucleated cell, Benzo(a)pyrene, Comutagenic, DMEM, Dulbeccos minimal essential medium, DMSO, dimethylsulfoxide, EROD, 7-ethoxyresorufin-O-deethylase, GST, glutathione-S-transferase, Hep G2/MN assay, LOAEL, lowest observed adverse effect level, M, mean, MK, musk ketone, MN, micronucleus, Musk ketone, NM, nitro musk, PAH, polycyclic aromatic hydrocarbon, PB, phenobarbital, S.D., standard deviation, UDPGT, uridine-diphosphate-glucuronyl-transferase.
Abstract
Musk ketone is a widely used artificial fragrance which has been identified in human fatty tissue and milk. The mutagenic and comutagenic effects of this compound were studied in micronucleus tests with a human derived hepatoma cell line (Hep G2). Exposure of the cells to MK alone in the range between 5 and 5000ng/ml did not cause induction of MN. When the cells were treated simultaneously with MK (5–5000ng/ml) and 0.2μg/ml benzo(a)pyrene, no synergistic effects were detected; benzo(a)pyrene (B(a)P) itself caused an 1.5-fold increase of MN over the spontaneous background frequency (60 versus 39 MN/1000 binucleated cells). In a third experimental series, the cells were pretreated with MK for 28h and subsequently exposed to 0.2μg/ml B(a)P. In this case, a pronounced comutagenic effect was observed: The LOAEL for MK was 0.05μg/ml. With higher doses (0.5, 1.0 and 5.0μg MK/ml), a significant increase of B(a)P induced MN frequencies was measured, the induction rates being 50, 66, and 88%, respectively. Additional measurements of 7-ethoxyresorufin deethylase indicated that MK induces cytochrome P450 isoenzymes (1A1) which play a key role in the activation of B(a)P. The results of the present study show that MK amplifies the genotoxic effects of B(a)P in human derived cells and indicate that exposure of humans to MK might increase their susceptibility to the health hazards of B(a)P and other polycyclic aromatic hydrocarbons.
Url:
DOI: 10.1016/S1383-5718(01)00202-9
Links to Exploration step
ISTEX:1F861B2B2A2AD2EAEADEBDCB70FE9FEB7524F0E9Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Musk ketone enhances benzo(a)pyrene induced mutagenicity in human derived Hep G2 cells</title><author><name sortKey="Mersch Sundermann, Volker" sort="Mersch Sundermann, Volker" uniqKey="Mersch Sundermann V" first="Volker" last="Mersch-Sundermann">Volker Mersch-Sundermann</name><affiliation><mods:affiliation>E-mail: mersch@rumms.uni-mannheim.de</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Toxicology and Ecotoxicology, FB VI, University of Trier, 54286 Trier, Germany</mods:affiliation></affiliation></author><author><name sortKey="Schneider, Heidi" sort="Schneider, Heidi" uniqKey="Schneider H" first="Heidi" last="Schneider">Heidi Schneider</name><affiliation><mods:affiliation>Faculty of Clinical Medicine Mannheim, Institute of Microbiology and Hygiene, University of Heidelberg, P.O. Box 100023, D-68135 Mannheim, Germany</mods:affiliation></affiliation></author><author><name sortKey="Freywald, Christian" sort="Freywald, Christian" uniqKey="Freywald C" first="Christian" last="Freywald">Christian Freywald</name><affiliation><mods:affiliation>Institute of Cancer Research, University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria</mods:affiliation></affiliation></author><author><name sortKey="Jenter, Cornelia" sort="Jenter, Cornelia" uniqKey="Jenter C" first="Cornelia" last="Jenter">Cornelia Jenter</name><affiliation><mods:affiliation>Faculty of Clinical Medicine Mannheim, Institute of Microbiology and Hygiene, University of Heidelberg, P.O. Box 100023, D-68135 Mannheim, Germany</mods:affiliation></affiliation></author><author><name sortKey="Parzefall, Wolfram" sort="Parzefall, Wolfram" uniqKey="Parzefall W" first="Wolfram" last="Parzefall">Wolfram Parzefall</name><affiliation><mods:affiliation>Faculty of Clinical Medicine Mannheim, Institute of Microbiology and Hygiene, University of Heidelberg, P.O. Box 100023, D-68135 Mannheim, Germany</mods:affiliation></affiliation></author><author><name sortKey="Knasmuller, Siegfried" sort="Knasmuller, Siegfried" uniqKey="Knasmuller S" first="Siegfried" last="Knasmüller">Siegfried Knasmüller</name><affiliation><mods:affiliation>Institute of Cancer Research, University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:1F861B2B2A2AD2EAEADEBDCB70FE9FEB7524F0E9</idno><date when="2001" year="2001">2001</date><idno type="doi">10.1016/S1383-5718(01)00202-9</idno><idno type="url">https://api.istex.fr/document/1F861B2B2A2AD2EAEADEBDCB70FE9FEB7524F0E9/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">001505</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001505</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Musk ketone enhances benzo(a)pyrene induced mutagenicity in human derived Hep G2 cells</title><author><name sortKey="Mersch Sundermann, Volker" sort="Mersch Sundermann, Volker" uniqKey="Mersch Sundermann V" first="Volker" last="Mersch-Sundermann">Volker Mersch-Sundermann</name><affiliation><mods:affiliation>E-mail: mersch@rumms.uni-mannheim.de</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Toxicology and Ecotoxicology, FB VI, University of Trier, 54286 Trier, Germany</mods:affiliation></affiliation></author><author><name sortKey="Schneider, Heidi" sort="Schneider, Heidi" uniqKey="Schneider H" first="Heidi" last="Schneider">Heidi Schneider</name><affiliation><mods:affiliation>Faculty of Clinical Medicine Mannheim, Institute of Microbiology and Hygiene, University of Heidelberg, P.O. Box 100023, D-68135 Mannheim, Germany</mods:affiliation></affiliation></author><author><name sortKey="Freywald, Christian" sort="Freywald, Christian" uniqKey="Freywald C" first="Christian" last="Freywald">Christian Freywald</name><affiliation><mods:affiliation>Institute of Cancer Research, University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria</mods:affiliation></affiliation></author><author><name sortKey="Jenter, Cornelia" sort="Jenter, Cornelia" uniqKey="Jenter C" first="Cornelia" last="Jenter">Cornelia Jenter</name><affiliation><mods:affiliation>Faculty of Clinical Medicine Mannheim, Institute of Microbiology and Hygiene, University of Heidelberg, P.O. Box 100023, D-68135 Mannheim, Germany</mods:affiliation></affiliation></author><author><name sortKey="Parzefall, Wolfram" sort="Parzefall, Wolfram" uniqKey="Parzefall W" first="Wolfram" last="Parzefall">Wolfram Parzefall</name><affiliation><mods:affiliation>Faculty of Clinical Medicine Mannheim, Institute of Microbiology and Hygiene, University of Heidelberg, P.O. Box 100023, D-68135 Mannheim, Germany</mods:affiliation></affiliation></author><author><name sortKey="Knasmuller, Siegfried" sort="Knasmuller, Siegfried" uniqKey="Knasmuller S" first="Siegfried" last="Knasmüller">Siegfried Knasmüller</name><affiliation><mods:affiliation>Institute of Cancer Research, University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Mutation Research - Genetic Toxicology and Environmental Mutagenesis</title><title level="j" type="abbrev">MUTGEN</title><idno type="ISSN">1383-5718</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2001">2001</date><biblScope unit="volume">495</biblScope><biblScope unit="issue">1–2</biblScope><biblScope unit="page" from="89">89</biblScope><biblScope unit="page" to="96">96</biblScope></imprint><idno type="ISSN">1383-5718</idno></series><idno type="istex">1F861B2B2A2AD2EAEADEBDCB70FE9FEB7524F0E9</idno><idno type="DOI">10.1016/S1383-5718(01)00202-9</idno><idno type="PII">S1383-5718(01)00202-9</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1383-5718</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>AC, Arochlor 1254</term><term>B(a)P, benzo(a)pyrene</term><term>BNC, binucleated cell</term><term>Benzo(a)pyrene</term><term>Comutagenic</term><term>DMEM, Dulbeccos minimal essential medium</term><term>DMSO, dimethylsulfoxide</term><term>EROD, 7-ethoxyresorufin-O-deethylase</term><term>GST, glutathione-S-transferase</term><term>Hep G2/MN assay</term><term>LOAEL, lowest observed adverse effect level</term><term>M, mean</term><term>MK, musk ketone</term><term>MN, micronucleus</term><term>Musk ketone</term><term>NM, nitro musk</term><term>PAH, polycyclic aromatic hydrocarbon</term><term>PB, phenobarbital</term><term>S.D., standard deviation</term><term>UDPGT, uridine-diphosphate-glucuronyl-transferase</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Musk ketone is a widely used artificial fragrance which has been identified in human fatty tissue and milk. The mutagenic and comutagenic effects of this compound were studied in micronucleus tests with a human derived hepatoma cell line (Hep G2). Exposure of the cells to MK alone in the range between 5 and 5000ng/ml did not cause induction of MN. When the cells were treated simultaneously with MK (5–5000ng/ml) and 0.2μg/ml benzo(a)pyrene, no synergistic effects were detected; benzo(a)pyrene (B(a)P) itself caused an 1.5-fold increase of MN over the spontaneous background frequency (60 versus 39 MN/1000 binucleated cells). In a third experimental series, the cells were pretreated with MK for 28h and subsequently exposed to 0.2μg/ml B(a)P. In this case, a pronounced comutagenic effect was observed: The LOAEL for MK was 0.05μg/ml. With higher doses (0.5, 1.0 and 5.0μg MK/ml), a significant increase of B(a)P induced MN frequencies was measured, the induction rates being 50, 66, and 88%, respectively. Additional measurements of 7-ethoxyresorufin deethylase indicated that MK induces cytochrome P450 isoenzymes (1A1) which play a key role in the activation of B(a)P. The results of the present study show that MK amplifies the genotoxic effects of B(a)P in human derived cells and indicate that exposure of humans to MK might increase their susceptibility to the health hazards of B(a)P and other polycyclic aromatic hydrocarbons.</div></front></TEI><istex><corpusName>elsevier</corpusName><author><json:item><name>Volker Mersch-Sundermann</name><affiliations><json:string>E-mail: mersch@rumms.uni-mannheim.de</json:string><json:string>Department of Toxicology and Ecotoxicology, FB VI, University of Trier, 54286 Trier, Germany</json:string></affiliations></json:item><json:item><name>Heidi Schneider</name><affiliations><json:string>Faculty of Clinical Medicine Mannheim, Institute of Microbiology and Hygiene, University of Heidelberg, P.O. Box 100023, D-68135 Mannheim, Germany</json:string></affiliations></json:item><json:item><name>Christian Freywald</name><affiliations><json:string>Institute of Cancer Research, University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria</json:string></affiliations></json:item><json:item><name>Cornelia Jenter</name><affiliations><json:string>Faculty of Clinical Medicine Mannheim, Institute of Microbiology and Hygiene, University of Heidelberg, P.O. Box 100023, D-68135 Mannheim, Germany</json:string></affiliations></json:item><json:item><name>Wolfram Parzefall</name><affiliations><json:string>Faculty of Clinical Medicine Mannheim, Institute of Microbiology and Hygiene, University of Heidelberg, P.O. Box 100023, D-68135 Mannheim, Germany</json:string></affiliations></json:item><json:item><name>Siegfried Knasmüller</name><affiliations><json:string>Institute of Cancer Research, University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>AC, Arochlor 1254</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>B(a)P, benzo(a)pyrene</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>BNC, binucleated cell</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>DMEM, Dulbeccos minimal essential medium</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>DMSO, dimethylsulfoxide</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>EROD, 7-ethoxyresorufin-O-deethylase</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>GST, glutathione-S-transferase</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>LOAEL, lowest observed adverse effect level</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>M, mean</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MK, musk ketone</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MN, micronucleus</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>NM, nitro musk</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PAH, polycyclic aromatic hydrocarbon</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PB, phenobarbital</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>S.D., standard deviation</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>UDPGT, uridine-diphosphate-glucuronyl-transferase</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Hep G2/MN assay</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Musk ketone</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Benzo(a)pyrene</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Comutagenic</value></json:item></subject><language><json:string>eng</json:string></language><originalGenre><json:string>Full-length article</json:string></originalGenre><abstract>Musk ketone is a widely used artificial fragrance which has been identified in human fatty tissue and milk. The mutagenic and comutagenic effects of this compound were studied in micronucleus tests with a human derived hepatoma cell line (Hep G2). Exposure of the cells to MK alone in the range between 5 and 5000ng/ml did not cause induction of MN. When the cells were treated simultaneously with MK (5–5000ng/ml) and 0.2μg/ml benzo(a)pyrene, no synergistic effects were detected; benzo(a)pyrene (B(a)P) itself caused an 1.5-fold increase of MN over the spontaneous background frequency (60 versus 39 MN/1000 binucleated cells). In a third experimental series, the cells were pretreated with MK for 28h and subsequently exposed to 0.2μg/ml B(a)P. In this case, a pronounced comutagenic effect was observed: The LOAEL for MK was 0.05μg/ml. With higher doses (0.5, 1.0 and 5.0μg MK/ml), a significant increase of B(a)P induced MN frequencies was measured, the induction rates being 50, 66, and 88%, respectively. Additional measurements of 7-ethoxyresorufin deethylase indicated that MK induces cytochrome P450 isoenzymes (1A1) which play a key role in the activation of B(a)P. The results of the present study show that MK amplifies the genotoxic effects of B(a)P in human derived cells and indicate that exposure of humans to MK might increase their susceptibility to the health hazards of B(a)P and other polycyclic aromatic hydrocarbons.</abstract><qualityIndicators><score>6.83</score><pdfVersion>1.2</pdfVersion><pdfPageSize>612 x 792 pts (letter)</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>20</keywordCount><abstractCharCount>1440</abstractCharCount><pdfWordCount>4154</pdfWordCount><pdfCharCount>25704</pdfCharCount><pdfPageCount>8</pdfPageCount><abstractWordCount>223</abstractWordCount></qualityIndicators><title>Musk ketone enhances benzo(a)pyrene induced mutagenicity in human derived Hep G2 cells</title><pii><json:string>S1383-5718(01)00202-9</json:string></pii><refBibs><json:item><author><json:item><name>J. 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Hep G2 cells were exposed (i) to different concentrations of MK for 28h (white bars), (ii) simultaneously to different MK concentrations and 0.2μg/ml B(a)P for 28h (hatched bars) or (iii) for 28h to different MK concentrations and subsequently to 0.2μg/ml B(a)P (black bars). After exposure, cells were cultivated for 24h in cytochalasin B supplemented medium, then the MN frequencies determined as described in the text. Three slides were prepared per experimental point and in total 1000 BNC were evaluated.</note><note type="content">Fig. 3: Effect of MK on the induction of EROD in Hep G2 cells: (a) the effect seen after exposure of the cells to different concentrations of MK; (b) the means±S.D. of three independent experiments in which the cells were exposed to either 1.0μg MK/ml or to the solvent only. The exposure time was 28h.</note><note type="content">Table 1: Effect of MK on MN frequencies in human Hep G2 cellsa</note><note type="content">Table 2: Effect of MK on the induction of MN by B(a)P in human Hep G2 cells (simultaneous treatment)a</note><note type="content">Table 3: Effect of MK pre-treatment on the induction of MN by B(a)P in human Hep G2 cellsa</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Musk ketone enhances benzo(a)pyrene induced mutagenicity in human derived Hep G2 cells</title><author xml:id="author-1"><persName><forename type="first">Volker</forename><surname>Mersch-Sundermann</surname></persName><email>mersch@rumms.uni-mannheim.de</email><note type="correspondence"><p>Corresponding author. Fax: +49-621-411278</p></note><affiliation>Department of Toxicology and Ecotoxicology, FB VI, University of Trier, 54286 Trier, Germany</affiliation></author><author xml:id="author-2"><persName><forename type="first">Heidi</forename><surname>Schneider</surname></persName><affiliation>Faculty of Clinical Medicine Mannheim, Institute of Microbiology and Hygiene, University of Heidelberg, P.O. Box 100023, D-68135 Mannheim, Germany</affiliation></author><author xml:id="author-3"><persName><forename type="first">Christian</forename><surname>Freywald</surname></persName><affiliation>Institute of Cancer Research, University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria</affiliation></author><author xml:id="author-4"><persName><forename type="first">Cornelia</forename><surname>Jenter</surname></persName><affiliation>Faculty of Clinical Medicine Mannheim, Institute of Microbiology and Hygiene, University of Heidelberg, P.O. Box 100023, D-68135 Mannheim, Germany</affiliation></author><author xml:id="author-5"><persName><forename type="first">Wolfram</forename><surname>Parzefall</surname></persName><affiliation>Faculty of Clinical Medicine Mannheim, Institute of Microbiology and Hygiene, University of Heidelberg, P.O. Box 100023, D-68135 Mannheim, Germany</affiliation></author><author xml:id="author-6"><persName><forename type="first">Siegfried</forename><surname>Knasmüller</surname></persName><affiliation>Institute of Cancer Research, University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria</affiliation></author></analytic><monogr><title level="j">Mutation Research - Genetic Toxicology and Environmental Mutagenesis</title><title level="j" type="abbrev">MUTGEN</title><idno type="pISSN">1383-5718</idno><idno type="PII">S1383-5718(00)X0071-X</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2001"></date><biblScope unit="volume">495</biblScope><biblScope unit="issue">1–2</biblScope><biblScope unit="page" from="89">89</biblScope><biblScope unit="page" to="96">96</biblScope></imprint></monogr><idno type="istex">1F861B2B2A2AD2EAEADEBDCB70FE9FEB7524F0E9</idno><idno type="DOI">10.1016/S1383-5718(01)00202-9</idno><idno type="PII">S1383-5718(01)00202-9</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2001</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Musk ketone is a widely used artificial fragrance which has been identified in human fatty tissue and milk. The mutagenic and comutagenic effects of this compound were studied in micronucleus tests with a human derived hepatoma cell line (Hep G2). Exposure of the cells to MK alone in the range between 5 and 5000ng/ml did not cause induction of MN. When the cells were treated simultaneously with MK (5–5000ng/ml) and 0.2μg/ml benzo(a)pyrene, no synergistic effects were detected; benzo(a)pyrene (B(a)P) itself caused an 1.5-fold increase of MN over the spontaneous background frequency (60 versus 39 MN/1000 binucleated cells). In a third experimental series, the cells were pretreated with MK for 28h and subsequently exposed to 0.2μg/ml B(a)P. In this case, a pronounced comutagenic effect was observed: The LOAEL for MK was 0.05μg/ml. With higher doses (0.5, 1.0 and 5.0μg MK/ml), a significant increase of B(a)P induced MN frequencies was measured, the induction rates being 50, 66, and 88%, respectively. Additional measurements of 7-ethoxyresorufin deethylase indicated that MK induces cytochrome P450 isoenzymes (1A1) which play a key role in the activation of B(a)P. The results of the present study show that MK amplifies the genotoxic effects of B(a)P in human derived cells and indicate that exposure of humans to MK might increase their susceptibility to the health hazards of B(a)P and other polycyclic aromatic hydrocarbons.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Abbreviations</head><item><term>AC, Arochlor 1254</term></item><item><term>B(a)P, benzo(a)pyrene</term></item><item><term>BNC, binucleated cell</term></item><item><term>DMEM, Dulbeccos minimal essential medium</term></item><item><term>DMSO, dimethylsulfoxide</term></item><item><term>EROD, 7-ethoxyresorufin-O-deethylase</term></item><item><term>GST, glutathione-S-transferase</term></item><item><term>LOAEL, lowest observed adverse effect level</term></item><item><term>M, mean</term></item><item><term>MK, musk ketone</term></item><item><term>MN, micronucleus</term></item><item><term>NM, nitro musk</term></item><item><term>PAH, polycyclic aromatic hydrocarbon</term></item><item><term>PB, phenobarbital</term></item><item><term>S.D., standard deviation</term></item><item><term>UDPGT, uridine-diphosphate-glucuronyl-transferase</term></item></list></keywords></textClass><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Hep G2/MN assay</term></item><item><term>Musk ketone</term></item><item><term>Benzo(a)pyrene</term></item><item><term>Comutagenic</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2001-05-08">Modified</change><change when="2001">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/1F861B2B2A2AD2EAEADEBDCB70FE9FEB7524F0E9/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: ce:floats; body; tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"><istex:entity SYSTEM="gr1" NDATA="IMAGE" name="gr1"></istex:entity><istex:entity SYSTEM="gr2" NDATA="IMAGE" name="gr2"></istex:entity><istex:entity SYSTEM="gr3" NDATA="IMAGE" name="gr3"></istex:entity></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla" xml:lang="en"><item-info><jid>MUTGEN</jid><aid>400292</aid><ce:pii>S1383-5718(01)00202-9</ce:pii><ce:doi>10.1016/S1383-5718(01)00202-9</ce:doi><ce:copyright type="full-transfer" year="2001">Elsevier Science B.V.</ce:copyright></item-info><head><ce:title>Musk ketone enhances benzo(a)pyrene induced mutagenicity in human derived Hep G2 cells</ce:title><ce:author-group><ce:author><ce:given-name>Volker</ce:given-name><ce:surname>Mersch-Sundermann</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref><ce:cross-ref refid="CORR1">*</ce:cross-ref><ce:e-address>mersch@rumms.uni-mannheim.de</ce:e-address></ce:author><ce:author><ce:given-name>Heidi</ce:given-name><ce:surname>Schneider</ce:surname><ce:cross-ref refid="AFF2"><ce:sup>b</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Christian</ce:given-name><ce:surname>Freywald</ce:surname><ce:cross-ref refid="AFF3"><ce:sup>c</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Cornelia</ce:given-name><ce:surname>Jenter</ce:surname><ce:cross-ref refid="AFF2"><ce:sup>b</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Wolfram</ce:given-name><ce:surname>Parzefall</ce:surname><ce:cross-ref refid="AFF2"><ce:sup>b</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Siegfried</ce:given-name><ce:surname>Knasmüller</ce:surname><ce:cross-ref refid="AFF3"><ce:sup>c</ce:sup></ce:cross-ref></ce:author><ce:affiliation id="AFF1"><ce:label>a</ce:label><ce:textfn>Department of Toxicology and Ecotoxicology, FB VI, University of Trier, 54286 Trier, Germany</ce:textfn></ce:affiliation><ce:affiliation id="AFF2"><ce:label>b</ce:label><ce:textfn>Faculty of Clinical Medicine Mannheim, Institute of Microbiology and Hygiene, University of Heidelberg, P.O. Box 100023, D-68135 Mannheim, Germany</ce:textfn></ce:affiliation><ce:affiliation id="AFF3"><ce:label>c</ce:label><ce:textfn>Institute of Cancer Research, University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria</ce:textfn></ce:affiliation><ce:correspondence id="CORR1"><ce:label>*</ce:label><ce:text>Corresponding author. Fax: +49-621-411278</ce:text></ce:correspondence></ce:author-group><ce:date-received day="20" month="2" year="2001"></ce:date-received><ce:date-revised day="8" month="5" year="2001"></ce:date-revised><ce:date-accepted day="10" month="5" year="2001"></ce:date-accepted><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>Musk ketone is a widely used artificial fragrance which has been identified in human fatty tissue and milk. The mutagenic and comutagenic effects of this compound were studied in micronucleus tests with a human derived hepatoma cell line (Hep G2). Exposure of the cells to MK alone in the range between 5 and 5000<ce:hsp sp="0.25"></ce:hsp>ng/ml did not cause induction of MN. When the cells were treated simultaneously with MK (5–5000<ce:hsp sp="0.25"></ce:hsp>ng/ml) and 0.2<ce:hsp sp="0.25"></ce:hsp>μg/ml benzo(a)pyrene, no synergistic effects were detected; benzo(a)pyrene (B(a)P) itself caused an 1.5-fold increase of MN over the spontaneous background frequency (60 versus 39 MN/1000 binucleated cells). In a third experimental series, the cells were pretreated with MK for 28<ce:hsp sp="0.25"></ce:hsp>h and subsequently exposed to 0.2<ce:hsp sp="0.25"></ce:hsp>μg/ml B(a)P. In this case, a pronounced comutagenic effect was observed: The LOAEL for MK was 0.05<ce:hsp sp="0.25"></ce:hsp>μg/ml. With higher doses (0.5, 1.0 and 5.0<ce:hsp sp="0.25"></ce:hsp>μg MK/ml), a significant increase of B(a)P induced MN frequencies was measured, the induction rates being 50, 66, and 88%, respectively. Additional measurements of 7-ethoxyresorufin deethylase indicated that MK induces cytochrome P450 isoenzymes (1A1) which play a key role in the activation of B(a)P. The results of the present study show that MK amplifies the genotoxic effects of B(a)P in human derived cells and indicate that exposure of humans to MK might increase their susceptibility to the health hazards of B(a)P and other polycyclic aromatic hydrocarbons.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords class="abr" xml:lang="en"><ce:section-title>Abbreviations</ce:section-title><ce:keyword><ce:text>AC, Arochlor 1254</ce:text></ce:keyword><ce:keyword><ce:text>B(a)P, benzo(a)pyrene</ce:text></ce:keyword><ce:keyword><ce:text>BNC, binucleated cell</ce:text></ce:keyword><ce:keyword><ce:text>DMEM, Dulbeccos minimal essential medium</ce:text></ce:keyword><ce:keyword><ce:text>DMSO, dimethylsulfoxide</ce:text></ce:keyword><ce:keyword><ce:text>EROD, 7-ethoxyresorufin-<ce:italic>O</ce:italic>-deethylase</ce:text></ce:keyword><ce:keyword><ce:text>GST, glutathione-<ce:italic>S</ce:italic>-transferase</ce:text></ce:keyword><ce:keyword><ce:text>LOAEL, lowest observed adverse effect level</ce:text></ce:keyword><ce:keyword><ce:text>M, mean</ce:text></ce:keyword><ce:keyword><ce:text>MK, musk ketone</ce:text></ce:keyword><ce:keyword><ce:text>MN, micronucleus</ce:text></ce:keyword><ce:keyword><ce:text>NM, nitro musk</ce:text></ce:keyword><ce:keyword><ce:text>PAH, polycyclic aromatic hydrocarbon</ce:text></ce:keyword><ce:keyword><ce:text>PB, phenobarbital</ce:text></ce:keyword><ce:keyword><ce:text>S.D., standard deviation</ce:text></ce:keyword><ce:keyword><ce:text>UDPGT, uridine-diphosphate-glucuronyl-transferase</ce:text></ce:keyword></ce:keywords><ce:keywords class="keyword" xml:lang="en"><ce:section-title>Keywords</ce:section-title><ce:keyword><ce:text>Hep G2/MN assay</ce:text></ce:keyword><ce:keyword><ce:text>Musk ketone</ce:text></ce:keyword><ce:keyword><ce:text>Benzo(a)pyrene</ce:text></ce:keyword><ce:keyword><ce:text>Comutagenic</ce:text></ce:keyword></ce:keywords></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Musk ketone enhances benzo(a)pyrene induced mutagenicity in human derived Hep G2 cells</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Musk ketone enhances benzo(a)pyrene induced mutagenicity in human derived Hep G2 cells</title></titleInfo><name type="personal"><namePart type="given">Volker</namePart><namePart type="family">Mersch-Sundermann</namePart><affiliation>E-mail: mersch@rumms.uni-mannheim.de</affiliation><affiliation>Department of Toxicology and Ecotoxicology, FB VI, University of Trier, 54286 Trier, Germany</affiliation><description>Corresponding author. Fax: +49-621-411278</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Heidi</namePart><namePart type="family">Schneider</namePart><affiliation>Faculty of Clinical Medicine Mannheim, Institute of Microbiology and Hygiene, University of Heidelberg, P.O. Box 100023, D-68135 Mannheim, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christian</namePart><namePart type="family">Freywald</namePart><affiliation>Institute of Cancer Research, University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Cornelia</namePart><namePart type="family">Jenter</namePart><affiliation>Faculty of Clinical Medicine Mannheim, Institute of Microbiology and Hygiene, University of Heidelberg, P.O. Box 100023, D-68135 Mannheim, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Wolfram</namePart><namePart type="family">Parzefall</namePart><affiliation>Faculty of Clinical Medicine Mannheim, Institute of Microbiology and Hygiene, University of Heidelberg, P.O. Box 100023, D-68135 Mannheim, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Siegfried</namePart><namePart type="family">Knasmüller</namePart><affiliation>Institute of Cancer Research, University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article"></genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">2001</dateIssued><dateModified encoding="w3cdtf">2001-05-08</dateModified><copyrightDate encoding="w3cdtf">2001</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract lang="en">Musk ketone is a widely used artificial fragrance which has been identified in human fatty tissue and milk. The mutagenic and comutagenic effects of this compound were studied in micronucleus tests with a human derived hepatoma cell line (Hep G2). Exposure of the cells to MK alone in the range between 5 and 5000ng/ml did not cause induction of MN. When the cells were treated simultaneously with MK (5–5000ng/ml) and 0.2μg/ml benzo(a)pyrene, no synergistic effects were detected; benzo(a)pyrene (B(a)P) itself caused an 1.5-fold increase of MN over the spontaneous background frequency (60 versus 39 MN/1000 binucleated cells). In a third experimental series, the cells were pretreated with MK for 28h and subsequently exposed to 0.2μg/ml B(a)P. In this case, a pronounced comutagenic effect was observed: The LOAEL for MK was 0.05μg/ml. With higher doses (0.5, 1.0 and 5.0μg MK/ml), a significant increase of B(a)P induced MN frequencies was measured, the induction rates being 50, 66, and 88%, respectively. Additional measurements of 7-ethoxyresorufin deethylase indicated that MK induces cytochrome P450 isoenzymes (1A1) which play a key role in the activation of B(a)P. The results of the present study show that MK amplifies the genotoxic effects of B(a)P in human derived cells and indicate that exposure of humans to MK might increase their susceptibility to the health hazards of B(a)P and other polycyclic aromatic hydrocarbons.</abstract><note type="content">Fig. 1: Chemical structure of musk ketone.</note><note type="content">Fig. 2: Induction of MN in Hep G2 cells by MK alone and in combination with B(a)P. Hep G2 cells were exposed (i) to different concentrations of MK for 28h (white bars), (ii) simultaneously to different MK concentrations and 0.2μg/ml B(a)P for 28h (hatched bars) or (iii) for 28h to different MK concentrations and subsequently to 0.2μg/ml B(a)P (black bars). After exposure, cells were cultivated for 24h in cytochalasin B supplemented medium, then the MN frequencies determined as described in the text. Three slides were prepared per experimental point and in total 1000 BNC were evaluated.</note><note type="content">Fig. 3: Effect of MK on the induction of EROD in Hep G2 cells: (a) the effect seen after exposure of the cells to different concentrations of MK; (b) the means±S.D. of three independent experiments in which the cells were exposed to either 1.0μg MK/ml or to the solvent only. The exposure time was 28h.</note><note type="content">Table 1: Effect of MK on MN frequencies in human Hep G2 cellsa</note><note type="content">Table 2: Effect of MK on the induction of MN by B(a)P in human Hep G2 cells (simultaneous treatment)a</note><note type="content">Table 3: Effect of MK pre-treatment on the induction of MN by B(a)P in human Hep G2 cellsa</note><subject lang="en"><genre>Abbreviations</genre><topic>AC, Arochlor 1254</topic><topic>B(a)P, benzo(a)pyrene</topic><topic>BNC, binucleated cell</topic><topic>DMEM, Dulbeccos minimal essential medium</topic><topic>DMSO, dimethylsulfoxide</topic><topic>EROD, 7-ethoxyresorufin-O-deethylase</topic><topic>GST, glutathione-S-transferase</topic><topic>LOAEL, lowest observed adverse effect level</topic><topic>M, mean</topic><topic>MK, musk ketone</topic><topic>MN, micronucleus</topic><topic>NM, nitro musk</topic><topic>PAH, polycyclic aromatic hydrocarbon</topic><topic>PB, phenobarbital</topic><topic>S.D., standard deviation</topic><topic>UDPGT, uridine-diphosphate-glucuronyl-transferase</topic></subject><subject lang="en"><genre>Keywords</genre><topic>Hep G2/MN assay</topic><topic>Musk ketone</topic><topic>Benzo(a)pyrene</topic><topic>Comutagenic</topic></subject><relatedItem type="host"><titleInfo><title>Mutation Research - Genetic Toxicology and Environmental Mutagenesis</title></titleInfo><titleInfo type="abbreviated"><title>MUTGEN</title></titleInfo><genre type="journal">journal</genre><originInfo><dateIssued encoding="w3cdtf">20010822</dateIssued></originInfo><identifier type="ISSN">1383-5718</identifier><identifier type="PII">S1383-5718(00)X0071-X</identifier><part><date>20010822</date><detail type="volume"><number>495</number><caption>vol.</caption></detail><detail type="issue"><number>1–2</number><caption>no.</caption></detail><extent unit="issue pages"><start>1</start><end>172</end></extent><extent unit="pages"><start>89</start><end>96</end></extent></part></relatedItem><identifier type="istex">1F861B2B2A2AD2EAEADEBDCB70FE9FEB7524F0E9</identifier><identifier type="DOI">10.1016/S1383-5718(01)00202-9</identifier><identifier type="PII">S1383-5718(01)00202-9</identifier><accessCondition type="use and reproduction" contentType="copyright">©2001 Elsevier Science B.V.</accessCondition><recordInfo><recordContentSource>ELSEVIER</recordContentSource><recordOrigin>Elsevier Science B.V., ©2001</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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