A recombinant model for assessing the role of GSTM1 in styrene-7,8-oxide toxicity and mutagenicity
Styrene-7,8-oxide (SO) is a highly reactive epoxide able to undergo reactions with endogenous nucleophiles, such as DNA. SO is inactivated by glutathione- S-transferase M1 (GSTM1). This detoxification enzyme is absent in approximately one-half of Caucasian (49%) populations. A GSTM1 recombinant huma...
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| Veröffentlicht in: | Toxicology (Amsterdam) 2004-01, Vol.195 (1), p.61-68 |
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| creator | Shield, Alison J. Sanderson, Barbara J.S. |
| description | Styrene-7,8-oxide (SO) is a highly reactive epoxide able to undergo reactions with endogenous nucleophiles, such as DNA. SO is inactivated by glutathione-
S-transferase M1 (GSTM1). This detoxification enzyme is absent in approximately one-half of Caucasian (49%) populations. A GSTM1 recombinant human lymphoblastoid cell line (FB7) was generated from a GSTM1 negative parental cell line (WIL2NS). GSTM1 status was determined using RT-PCR and immunochemistry. Cells were challenged with a range of SO doses and subsequent toxicity (population growth in flasks) and genotoxicity (mutations at the HPRT locus) were monitored. FB7 (GSTM1 positive) exhibited greater cell survival after SO exposure relative to the GSTM1 negative parental line. The IC
50 following a 1
h exposure to SO was 0.5
mM for WIL2NS, compared to greater than 2.5
mM for FB7. The extrapolated IC
50 for FB7 was 5.5
mM. Significantly fewer mutant cells were induced by SO for FB7 than for WIL2NS at equivalent doses of SO. These findings suggest that the sensitivity of cells to styrene-7,8-oxide is influenced by GSTM1 status and that a recombinant GSTM1 positive cell line can efficiently detoxify styrene-7,8-oxide. |
| doi_str_mv | 10.1016/j.tox.2003.08.010 |
| format | Article |
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S-transferase M1 (GSTM1). This detoxification enzyme is absent in approximately one-half of Caucasian (49%) populations. A GSTM1 recombinant human lymphoblastoid cell line (FB7) was generated from a GSTM1 negative parental cell line (WIL2NS). GSTM1 status was determined using RT-PCR and immunochemistry. Cells were challenged with a range of SO doses and subsequent toxicity (population growth in flasks) and genotoxicity (mutations at the HPRT locus) were monitored. FB7 (GSTM1 positive) exhibited greater cell survival after SO exposure relative to the GSTM1 negative parental line. The IC
50 following a 1
h exposure to SO was 0.5
mM for WIL2NS, compared to greater than 2.5
mM for FB7. The extrapolated IC
50 for FB7 was 5.5
mM. Significantly fewer mutant cells were induced by SO for FB7 than for WIL2NS at equivalent doses of SO. These findings suggest that the sensitivity of cells to styrene-7,8-oxide is influenced by GSTM1 status and that a recombinant GSTM1 positive cell line can efficiently detoxify styrene-7,8-oxide.</description><identifier>ISSN: 0300-483X</identifier><identifier>EISSN: 1879-3185</identifier><identifier>DOI: 10.1016/j.tox.2003.08.010</identifier><identifier>PMID: 14698568</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Cell Survival - drug effects ; Cell Survival - genetics ; Dose-Response Relationship, Drug ; Epoxy Compounds - toxicity ; Genotype ; Glutathione Transferase - genetics ; Glutathione Transferase - metabolism ; Glutathione- S-transferase M1 ; Humans ; Inhibitory Concentration 50 ; Mutagenicity ; Mutagenicity Tests ; Mutagens - toxicity ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology ; Recombinant cells ; Recombinant Proteins - genetics ; Recombinant Proteins - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Styrene-7,8-oxide ; Toxicity ; Tumor Cells, Cultured</subject><ispartof>Toxicology (Amsterdam), 2004-01, Vol.195 (1), p.61-68</ispartof><rights>2003 Elsevier Ireland Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c477t-173606b75025206bc64babead12a2428dcaf0f7192307fc7d5fea6ffc82832383</citedby><cites>FETCH-LOGICAL-c477t-173606b75025206bc64babead12a2428dcaf0f7192307fc7d5fea6ffc82832383</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0300483X03004116$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14698568$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shield, Alison J.</creatorcontrib><creatorcontrib>Sanderson, Barbara J.S.</creatorcontrib><title>A recombinant model for assessing the role of GSTM1 in styrene-7,8-oxide toxicity and mutagenicity</title><title>Toxicology (Amsterdam)</title><addtitle>Toxicology</addtitle><description>Styrene-7,8-oxide (SO) is a highly reactive epoxide able to undergo reactions with endogenous nucleophiles, such as DNA. SO is inactivated by glutathione-
S-transferase M1 (GSTM1). This detoxification enzyme is absent in approximately one-half of Caucasian (49%) populations. A GSTM1 recombinant human lymphoblastoid cell line (FB7) was generated from a GSTM1 negative parental cell line (WIL2NS). GSTM1 status was determined using RT-PCR and immunochemistry. Cells were challenged with a range of SO doses and subsequent toxicity (population growth in flasks) and genotoxicity (mutations at the HPRT locus) were monitored. FB7 (GSTM1 positive) exhibited greater cell survival after SO exposure relative to the GSTM1 negative parental line. The IC
50 following a 1
h exposure to SO was 0.5
mM for WIL2NS, compared to greater than 2.5
mM for FB7. The extrapolated IC
50 for FB7 was 5.5
mM. Significantly fewer mutant cells were induced by SO for FB7 than for WIL2NS at equivalent doses of SO. These findings suggest that the sensitivity of cells to styrene-7,8-oxide is influenced by GSTM1 status and that a recombinant GSTM1 positive cell line can efficiently detoxify styrene-7,8-oxide.</description><subject>Cell Survival - drug effects</subject><subject>Cell Survival - genetics</subject><subject>Dose-Response Relationship, Drug</subject><subject>Epoxy Compounds - toxicity</subject><subject>Genotype</subject><subject>Glutathione Transferase - genetics</subject><subject>Glutathione Transferase - metabolism</subject><subject>Glutathione- S-transferase M1</subject><subject>Humans</subject><subject>Inhibitory Concentration 50</subject><subject>Mutagenicity</subject><subject>Mutagenicity Tests</subject><subject>Mutagens - toxicity</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology</subject><subject>Recombinant cells</subject><subject>Recombinant Proteins - genetics</subject><subject>Recombinant Proteins - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Styrene-7,8-oxide</subject><subject>Toxicity</subject><subject>Tumor Cells, Cultured</subject><issn>0300-483X</issn><issn>1879-3185</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFv1DAQhS0EotvCD-CCfOJEwthObEecqgpapCIOFImb5djj4lViFzuLuv-eLLsSNzjNaPS9p5l5hLxi0DJg8t22XfJjywFEC7oFBk_Ihmk1NILp_inZgABoOi2-n5HzWrcAwEUnn5Mz1slB91JvyHhJC7o8jzHZtNA5e5xoyIXaWrHWmO7p8gNpyRPSHOj117vPjMZE67IvmLBRb3WTH6NHuq4SXVz21CZP591i7zH9Gbwgz4KdKr481Qvy7eOHu6ub5vbL9aery9vGdUotDVNCghxVD7zna-NkN9oRrWfc8o5r72yAoNjABajglO8DWhmC01wLLrS4IG-Ovg8l_9xhXcwcq8NpsgnzrpqDUgxy-D_YSd0r0a0gO4Ku5FoLBvNQ4mzL3jAwhwTM1qxnm0MCBrRZE1g1r0_mu3FG_1dxevkKvD8CuP7iV8RiqouYHPq4JrEYn-M_7H8DCKOWaQ</recordid><startdate>20040115</startdate><enddate>20040115</enddate><creator>Shield, Alison J.</creator><creator>Sanderson, Barbara J.S.</creator><general>Elsevier Ireland Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7ST</scope><scope>C1K</scope><scope>SOI</scope><scope>7U7</scope></search><sort><creationdate>20040115</creationdate><title>A recombinant model for assessing the role of GSTM1 in styrene-7,8-oxide toxicity and mutagenicity</title><author>Shield, Alison J. ; Sanderson, Barbara J.S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c477t-173606b75025206bc64babead12a2428dcaf0f7192307fc7d5fea6ffc82832383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Cell Survival - drug effects</topic><topic>Cell Survival - genetics</topic><topic>Dose-Response Relationship, Drug</topic><topic>Epoxy Compounds - toxicity</topic><topic>Genotype</topic><topic>Glutathione Transferase - genetics</topic><topic>Glutathione Transferase - metabolism</topic><topic>Glutathione- S-transferase M1</topic><topic>Humans</topic><topic>Inhibitory Concentration 50</topic><topic>Mutagenicity</topic><topic>Mutagenicity Tests</topic><topic>Mutagens - toxicity</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology</topic><topic>Recombinant cells</topic><topic>Recombinant Proteins - genetics</topic><topic>Recombinant Proteins - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Styrene-7,8-oxide</topic><topic>Toxicity</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shield, Alison J.</creatorcontrib><creatorcontrib>Sanderson, Barbara J.S.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Environment Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Environment Abstracts</collection><collection>Toxicology Abstracts</collection><jtitle>Toxicology (Amsterdam)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shield, Alison J.</au><au>Sanderson, Barbara J.S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A recombinant model for assessing the role of GSTM1 in styrene-7,8-oxide toxicity and mutagenicity</atitle><jtitle>Toxicology (Amsterdam)</jtitle><addtitle>Toxicology</addtitle><date>2004-01-15</date><risdate>2004</risdate><volume>195</volume><issue>1</issue><spage>61</spage><epage>68</epage><pages>61-68</pages><issn>0300-483X</issn><eissn>1879-3185</eissn><abstract>Styrene-7,8-oxide (SO) is a highly reactive epoxide able to undergo reactions with endogenous nucleophiles, such as DNA. SO is inactivated by glutathione-
S-transferase M1 (GSTM1). This detoxification enzyme is absent in approximately one-half of Caucasian (49%) populations. A GSTM1 recombinant human lymphoblastoid cell line (FB7) was generated from a GSTM1 negative parental cell line (WIL2NS). GSTM1 status was determined using RT-PCR and immunochemistry. Cells were challenged with a range of SO doses and subsequent toxicity (population growth in flasks) and genotoxicity (mutations at the HPRT locus) were monitored. FB7 (GSTM1 positive) exhibited greater cell survival after SO exposure relative to the GSTM1 negative parental line. The IC
50 following a 1
h exposure to SO was 0.5
mM for WIL2NS, compared to greater than 2.5
mM for FB7. The extrapolated IC
50 for FB7 was 5.5
mM. Significantly fewer mutant cells were induced by SO for FB7 than for WIL2NS at equivalent doses of SO. These findings suggest that the sensitivity of cells to styrene-7,8-oxide is influenced by GSTM1 status and that a recombinant GSTM1 positive cell line can efficiently detoxify styrene-7,8-oxide.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>14698568</pmid><doi>10.1016/j.tox.2003.08.010</doi><tpages>8</tpages></addata></record> |
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| subjects | Cell Survival - drug effects Cell Survival - genetics Dose-Response Relationship, Drug Epoxy Compounds - toxicity Genotype Glutathione Transferase - genetics Glutathione Transferase - metabolism Glutathione- S-transferase M1 Humans Inhibitory Concentration 50 Mutagenicity Mutagenicity Tests Mutagens - toxicity Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology Recombinant cells Recombinant Proteins - genetics Recombinant Proteins - metabolism Reverse Transcriptase Polymerase Chain Reaction Styrene-7,8-oxide Toxicity Tumor Cells, Cultured |
| title | A recombinant model for assessing the role of GSTM1 in styrene-7,8-oxide toxicity and mutagenicity |
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