Ku80 Deficiency Does Not Affect Particulate Chromate–Induced Chromosome Damage and Cytotoxicity in Chinese Hamster Ovary Cells
Particulate hexavalent chromium ((Cr(VI)) compounds are human lung carcinogens. These compounds induce DNA damage, chromosome aberrations, and concentration-dependent cell death in human and Chinese hamster ovary (CHO) cells. The relationship between Cr(VI)-induced DNA damage and chromosome aberrati...
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| Veröffentlicht in: | Toxicological sciences 2007-06, Vol.97 (2), p.348-354 |
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| creator | Camyre, Eric Wise, Sandra S. Milligan, Peter Gordon, Nancy Goodale, Britton Stackpole, Megan Patzlaff, Natalie Aboueissa, AbouEl-Makarim Wise, John Pierce |
| description | Particulate hexavalent chromium ((Cr(VI)) compounds are human lung carcinogens. These compounds induce DNA damage, chromosome aberrations, and concentration-dependent cell death in human and Chinese hamster ovary (CHO) cells. The relationship between Cr(VI)-induced DNA damage and chromosome aberrations is poorly understood. Accordingly, this study focused on examining the role of Ku80, a gene involved in nonhomologous end-joining repair, in particulate chromate–induced cytotoxicity and chromosome damage in CHO cells. Three different cell lines were used: CHO-K1 (parental), xrs-6 (Ku80 deficient), and 2E (xrs-6 complemented with Ku80 gene). Levels of cell death were higher in xrs-6 cells when compared to wild type, suggesting that Ku80 was important for protecting cells from lead chromate. However, Ku80 played no role in protecting cells from particulate Cr(VI)-induced chromosome instability (CIN) as gene complementation with Ku80 (2E cells) studies and uptake experiments showed similar frequency and amounts of chromosome damage between the cell lines and that any observed difference based on administered concentration was actually due to differences in Cr(VI) uptake. The spectrum of chromosome damage was also unaffected by Ku80 deficiency. These data indicate that Ku80 protects cells from cytotoxicity but is not involved in protecting cells from particulate chromate–induced CIN. |
| doi_str_mv | 10.1093/toxsci/kfm045 |
| format | Article |
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These compounds induce DNA damage, chromosome aberrations, and concentration-dependent cell death in human and Chinese hamster ovary (CHO) cells. The relationship between Cr(VI)-induced DNA damage and chromosome aberrations is poorly understood. Accordingly, this study focused on examining the role of Ku80, a gene involved in nonhomologous end-joining repair, in particulate chromate–induced cytotoxicity and chromosome damage in CHO cells. Three different cell lines were used: CHO-K1 (parental), xrs-6 (Ku80 deficient), and 2E (xrs-6 complemented with Ku80 gene). Levels of cell death were higher in xrs-6 cells when compared to wild type, suggesting that Ku80 was important for protecting cells from lead chromate. However, Ku80 played no role in protecting cells from particulate Cr(VI)-induced chromosome instability (CIN) as gene complementation with Ku80 (2E cells) studies and uptake experiments showed similar frequency and amounts of chromosome damage between the cell lines and that any observed difference based on administered concentration was actually due to differences in Cr(VI) uptake. The spectrum of chromosome damage was also unaffected by Ku80 deficiency. These data indicate that Ku80 protects cells from cytotoxicity but is not involved in protecting cells from particulate chromate–induced CIN.</description><identifier>ISSN: 1096-6080</identifier><identifier>EISSN: 1096-0929</identifier><identifier>DOI: 10.1093/toxsci/kfm045</identifier><identifier>PMID: 17361020</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Animals ; Antigens, Nuclear - genetics ; Cell Line ; Cell Survival - drug effects ; CHO Cells ; chromate ; Chromates - chemistry ; Chromates - toxicity ; chromium ; Chromium - metabolism ; Chromosome Breakage - drug effects ; chromosome instability ; Chromosomes - drug effects ; Chromosomes - ultrastructure ; Cricetinae ; Cricetulus ; DNA Repair - drug effects ; DNA Repair - genetics ; DNA-Binding Proteins - genetics ; Indicators and Reagents ; Ku Autoantigen ; Ku80 ; Lead - chemistry ; Lead - toxicity ; Mutagenicity Tests ; nonhomologous end-joining repair ; particulate ; single-strand breaks</subject><ispartof>Toxicological sciences, 2007-06, Vol.97 (2), p.348-354</ispartof><rights>The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c432t-e7daee7070fefb59834cabce5bdbaca8805136b1cee16cd33e4d3ab36a1fc8c23</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1578,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17361020$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Camyre, Eric</creatorcontrib><creatorcontrib>Wise, Sandra S.</creatorcontrib><creatorcontrib>Milligan, Peter</creatorcontrib><creatorcontrib>Gordon, Nancy</creatorcontrib><creatorcontrib>Goodale, Britton</creatorcontrib><creatorcontrib>Stackpole, Megan</creatorcontrib><creatorcontrib>Patzlaff, Natalie</creatorcontrib><creatorcontrib>Aboueissa, AbouEl-Makarim</creatorcontrib><creatorcontrib>Wise, John Pierce</creatorcontrib><title>Ku80 Deficiency Does Not Affect Particulate Chromate–Induced Chromosome Damage and Cytotoxicity in Chinese Hamster Ovary Cells</title><title>Toxicological sciences</title><addtitle>Toxicol Sci</addtitle><description>Particulate hexavalent chromium ((Cr(VI)) compounds are human lung carcinogens. These compounds induce DNA damage, chromosome aberrations, and concentration-dependent cell death in human and Chinese hamster ovary (CHO) cells. The relationship between Cr(VI)-induced DNA damage and chromosome aberrations is poorly understood. Accordingly, this study focused on examining the role of Ku80, a gene involved in nonhomologous end-joining repair, in particulate chromate–induced cytotoxicity and chromosome damage in CHO cells. Three different cell lines were used: CHO-K1 (parental), xrs-6 (Ku80 deficient), and 2E (xrs-6 complemented with Ku80 gene). Levels of cell death were higher in xrs-6 cells when compared to wild type, suggesting that Ku80 was important for protecting cells from lead chromate. However, Ku80 played no role in protecting cells from particulate Cr(VI)-induced chromosome instability (CIN) as gene complementation with Ku80 (2E cells) studies and uptake experiments showed similar frequency and amounts of chromosome damage between the cell lines and that any observed difference based on administered concentration was actually due to differences in Cr(VI) uptake. The spectrum of chromosome damage was also unaffected by Ku80 deficiency. These data indicate that Ku80 protects cells from cytotoxicity but is not involved in protecting cells from particulate chromate–induced CIN.</description><subject>Animals</subject><subject>Antigens, Nuclear - genetics</subject><subject>Cell Line</subject><subject>Cell Survival - drug effects</subject><subject>CHO Cells</subject><subject>chromate</subject><subject>Chromates - chemistry</subject><subject>Chromates - toxicity</subject><subject>chromium</subject><subject>Chromium - metabolism</subject><subject>Chromosome Breakage - drug effects</subject><subject>chromosome instability</subject><subject>Chromosomes - drug effects</subject><subject>Chromosomes - ultrastructure</subject><subject>Cricetinae</subject><subject>Cricetulus</subject><subject>DNA Repair - drug effects</subject><subject>DNA Repair - genetics</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Indicators and Reagents</subject><subject>Ku Autoantigen</subject><subject>Ku80</subject><subject>Lead - chemistry</subject><subject>Lead - toxicity</subject><subject>Mutagenicity Tests</subject><subject>nonhomologous end-joining repair</subject><subject>particulate</subject><subject>single-strand breaks</subject><issn>1096-6080</issn><issn>1096-0929</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMFu1DAURa2KipaBJVvkFWIT-hwnTrIsMy1TtWorBKLqxnKcZzCdxIPtoM6u_9A_5EswSkSXrPx0dXR9dQh5zeA9g4YfRXcftD26Mz0U5R45TKHIoMmbZ_MtoIYD8iKEHwCMCWiekwNWccEgh0PycD7WQFdorLY46B1dOQz00kV6bAzqSK-Vj1aPGxWRLr9716fj98Pj2dCNGrspcsH1SFeqV9-QqiGlu-jSsNQZd9QOibIDBqRr1YeInl79Un5Hl7jZhJdk36hNwFfzuyBfTk8-L9fZxdXHs-XxRaYLnscMq04hVlCBQdOWTc0LrVqNZdu1Squ6hpJx0TKNyITuOMei46rlQjGja53zBXk79W69-zliiLK3QacFakA3BsmaGoRIvQuSTaD2LgSPRm697dNeyUD-VS4n5XJSnvg3c_HY9tg90bPjBLybADdu_9s1_22Tpvt_sPJ3UlS8KuX65lZ-KC6_frrNr2XJ_wDFd5_g</recordid><startdate>20070601</startdate><enddate>20070601</enddate><creator>Camyre, Eric</creator><creator>Wise, Sandra S.</creator><creator>Milligan, Peter</creator><creator>Gordon, Nancy</creator><creator>Goodale, Britton</creator><creator>Stackpole, Megan</creator><creator>Patzlaff, Natalie</creator><creator>Aboueissa, AbouEl-Makarim</creator><creator>Wise, John Pierce</creator><general>Oxford University Press</general><scope>BSCLL</scope><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>7TM</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20070601</creationdate><title>Ku80 Deficiency Does Not Affect Particulate Chromate–Induced Chromosome Damage and Cytotoxicity in Chinese Hamster Ovary Cells</title><author>Camyre, Eric ; Wise, Sandra S. ; Milligan, Peter ; Gordon, Nancy ; Goodale, Britton ; Stackpole, Megan ; Patzlaff, Natalie ; Aboueissa, AbouEl-Makarim ; Wise, John Pierce</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c432t-e7daee7070fefb59834cabce5bdbaca8805136b1cee16cd33e4d3ab36a1fc8c23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Antigens, Nuclear - genetics</topic><topic>Cell Line</topic><topic>Cell Survival - drug effects</topic><topic>CHO Cells</topic><topic>chromate</topic><topic>Chromates - chemistry</topic><topic>Chromates - toxicity</topic><topic>chromium</topic><topic>Chromium - metabolism</topic><topic>Chromosome Breakage - drug effects</topic><topic>chromosome instability</topic><topic>Chromosomes - drug effects</topic><topic>Chromosomes - ultrastructure</topic><topic>Cricetinae</topic><topic>Cricetulus</topic><topic>DNA Repair - drug effects</topic><topic>DNA Repair - genetics</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Indicators and Reagents</topic><topic>Ku Autoantigen</topic><topic>Ku80</topic><topic>Lead - chemistry</topic><topic>Lead - toxicity</topic><topic>Mutagenicity Tests</topic><topic>nonhomologous end-joining repair</topic><topic>particulate</topic><topic>single-strand breaks</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Camyre, Eric</creatorcontrib><creatorcontrib>Wise, Sandra S.</creatorcontrib><creatorcontrib>Milligan, Peter</creatorcontrib><creatorcontrib>Gordon, Nancy</creatorcontrib><creatorcontrib>Goodale, Britton</creatorcontrib><creatorcontrib>Stackpole, Megan</creatorcontrib><creatorcontrib>Patzlaff, Natalie</creatorcontrib><creatorcontrib>Aboueissa, AbouEl-Makarim</creatorcontrib><creatorcontrib>Wise, John Pierce</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Toxicological sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Camyre, Eric</au><au>Wise, Sandra S.</au><au>Milligan, Peter</au><au>Gordon, Nancy</au><au>Goodale, Britton</au><au>Stackpole, Megan</au><au>Patzlaff, Natalie</au><au>Aboueissa, AbouEl-Makarim</au><au>Wise, John Pierce</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ku80 Deficiency Does Not Affect Particulate Chromate–Induced Chromosome Damage and Cytotoxicity in Chinese Hamster Ovary Cells</atitle><jtitle>Toxicological sciences</jtitle><addtitle>Toxicol Sci</addtitle><date>2007-06-01</date><risdate>2007</risdate><volume>97</volume><issue>2</issue><spage>348</spage><epage>354</epage><pages>348-354</pages><issn>1096-6080</issn><eissn>1096-0929</eissn><abstract>Particulate hexavalent chromium ((Cr(VI)) compounds are human lung carcinogens. These compounds induce DNA damage, chromosome aberrations, and concentration-dependent cell death in human and Chinese hamster ovary (CHO) cells. The relationship between Cr(VI)-induced DNA damage and chromosome aberrations is poorly understood. Accordingly, this study focused on examining the role of Ku80, a gene involved in nonhomologous end-joining repair, in particulate chromate–induced cytotoxicity and chromosome damage in CHO cells. Three different cell lines were used: CHO-K1 (parental), xrs-6 (Ku80 deficient), and 2E (xrs-6 complemented with Ku80 gene). Levels of cell death were higher in xrs-6 cells when compared to wild type, suggesting that Ku80 was important for protecting cells from lead chromate. However, Ku80 played no role in protecting cells from particulate Cr(VI)-induced chromosome instability (CIN) as gene complementation with Ku80 (2E cells) studies and uptake experiments showed similar frequency and amounts of chromosome damage between the cell lines and that any observed difference based on administered concentration was actually due to differences in Cr(VI) uptake. The spectrum of chromosome damage was also unaffected by Ku80 deficiency. These data indicate that Ku80 protects cells from cytotoxicity but is not involved in protecting cells from particulate chromate–induced CIN.</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>17361020</pmid><doi>10.1093/toxsci/kfm045</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Animals Antigens, Nuclear - genetics Cell Line Cell Survival - drug effects CHO Cells chromate Chromates - chemistry Chromates - toxicity chromium Chromium - metabolism Chromosome Breakage - drug effects chromosome instability Chromosomes - drug effects Chromosomes - ultrastructure Cricetinae Cricetulus DNA Repair - drug effects DNA Repair - genetics DNA-Binding Proteins - genetics Indicators and Reagents Ku Autoantigen Ku80 Lead - chemistry Lead - toxicity Mutagenicity Tests nonhomologous end-joining repair particulate single-strand breaks |
| title | Ku80 Deficiency Does Not Affect Particulate Chromate–Induced Chromosome Damage and Cytotoxicity in Chinese Hamster Ovary Cells |
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