Quantitative Analysis of Multiple Exocyclic DNA Adducts in Human Salivary DNA by Stable Isotope Dilution Nanoflow Liquid Chromatography–Nanospray Ionization Tandem Mass Spectrometry
Exocyclic DNA adducts, including 1,N 2-propano-2′-deoxyguanosine derived from acrolein (AdG) and crotonaldehyde (CdG) and the three lipid peroxidation-related etheno adducts 1,N 6-etheno-2′-deoxyadenosine (εdAdo), 3,N 4-etheno-2′-deoxycytidine (εdCyt), and 1,N 2-etheno-2′-deoxyguanosine (1,N 2-εdGuo...
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| Veröffentlicht in: | Analytical chemistry (Washington) 2011-11, Vol.83 (22), p.8543-8551 |
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| description | Exocyclic DNA adducts, including 1,N 2-propano-2′-deoxyguanosine derived from acrolein (AdG) and crotonaldehyde (CdG) and the three lipid peroxidation-related etheno adducts 1,N 6-etheno-2′-deoxyadenosine (εdAdo), 3,N 4-etheno-2′-deoxycytidine (εdCyt), and 1,N 2-etheno-2′-deoxyguanosine (1,N 2-εdGuo), play an important role in cancer formation and they are associated with oxidative-stress-induced DNA damage. Saliva is an easily accessible and available biological fluid and a potential target of noninvasive biomarkers. In this study, a highly sensitive and specific assay based on isotope dilution nanoflow LC–nanospray ionization tandem mass spectrometry (nanoLC–NSI/MS/MS) is developed for simultaneous detection and quantification of these five adducts in human salivary DNA. The levels of AdG, CdG, εdAdo, εdCyd, and 1,N 2-εdGuo, measured in 27 human salivary DNA samples from healthy volunteers, were determined as 104 ± 50, 7.6 ± 12, 99 ± 50, 72 ± 49, 391 ± 198 (mean ± SD) in 108 normal nucleotides, respectively, starting with 25 μg of DNA isolated from an average of 3 mL of saliva. Statistically significant correlations were found between levels of εdAdo and εdCyd (γ = 0.8007, p < 0.0001), between levels of εdAdo and 1,N 2-εdGuo (γ = 0.6778, p = 0.0001), between levels of εdCyd and 1,N 2-εdGuo (γ = 0.5643, p = 0.0022), between levels of AdG and 1,N 2-εdGuo (γ = 0.5756, p = 0.0017), and between levels of AdG and εdAdo (γ = 0.3969, p = 0.0404). Only 5 μg of DNA sample was analyzed for simultaneous quantification of these adducts. The easy accessibility and availability of saliva and the requirement for the small amount of DNA samples make this nanoLC–NSI/MS/MS assay clinically feasible in assessing the possibility of measuring 1,N 2-propano-2′-deoxyguanosine and etheno adducts levels in human salivary DNA as noninvasive biomarkers for DNA damage resulting from oxidative stress and for evaluating their roles in cancer formation and prevention. |
| doi_str_mv | 10.1021/ac201874d |
| format | Article |
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Saliva is an easily accessible and available biological fluid and a potential target of noninvasive biomarkers. In this study, a highly sensitive and specific assay based on isotope dilution nanoflow LC–nanospray ionization tandem mass spectrometry (nanoLC–NSI/MS/MS) is developed for simultaneous detection and quantification of these five adducts in human salivary DNA. The levels of AdG, CdG, εdAdo, εdCyd, and 1,N 2-εdGuo, measured in 27 human salivary DNA samples from healthy volunteers, were determined as 104 ± 50, 7.6 ± 12, 99 ± 50, 72 ± 49, 391 ± 198 (mean ± SD) in 108 normal nucleotides, respectively, starting with 25 μg of DNA isolated from an average of 3 mL of saliva. Statistically significant correlations were found between levels of εdAdo and εdCyd (γ = 0.8007, p < 0.0001), between levels of εdAdo and 1,N 2-εdGuo (γ = 0.6778, p = 0.0001), between levels of εdCyd and 1,N 2-εdGuo (γ = 0.5643, p = 0.0022), between levels of AdG and 1,N 2-εdGuo (γ = 0.5756, p = 0.0017), and between levels of AdG and εdAdo (γ = 0.3969, p = 0.0404). Only 5 μg of DNA sample was analyzed for simultaneous quantification of these adducts. The easy accessibility and availability of saliva and the requirement for the small amount of DNA samples make this nanoLC–NSI/MS/MS assay clinically feasible in assessing the possibility of measuring 1,N 2-propano-2′-deoxyguanosine and etheno adducts levels in human salivary DNA as noninvasive biomarkers for DNA damage resulting from oxidative stress and for evaluating their roles in cancer formation and prevention.</description><identifier>ISSN: 0003-2700</identifier><identifier>EISSN: 1520-6882</identifier><identifier>DOI: 10.1021/ac201874d</identifier><identifier>PMID: 21958347</identifier><identifier>CODEN: ANCHAM</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Analytical chemistry ; Body fluids ; Chemistry ; Chromatographic methods and physical methods associated with chromatography ; Chromatography, Liquid ; Correlation analysis ; DNA Adducts - analysis ; DNA Adducts - chemistry ; DNA damage ; Exact sciences and technology ; Humans ; Indicator Dilution Techniques ; Isotopes ; Lipids ; Nanotechnology - methods ; Other chromatographic methods ; Oxidative stress ; Reference Values ; Salivary Glands - metabolism ; Spectrometric and optical methods ; Tandem Mass Spectrometry</subject><ispartof>Analytical chemistry (Washington), 2011-11, Vol.83 (22), p.8543-8551</ispartof><rights>Copyright © 2011 American Chemical Society</rights><rights>2015 INIST-CNRS</rights><rights>Copyright American Chemical Society Nov 15, 2011</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a437t-32adc801572473558208ccd87b9bf2384d29953aa334d2fd731dc8c3f6f4fca93</citedby><cites>FETCH-LOGICAL-a437t-32adc801572473558208ccd87b9bf2384d29953aa334d2fd731dc8c3f6f4fca93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/ac201874d$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/ac201874d$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24770364$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21958347$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Hauh-Jyun Candy</creatorcontrib><creatorcontrib>Lin, Wen-Peng</creatorcontrib><title>Quantitative Analysis of Multiple Exocyclic DNA Adducts in Human Salivary DNA by Stable Isotope Dilution Nanoflow Liquid Chromatography–Nanospray Ionization Tandem Mass Spectrometry</title><title>Analytical chemistry (Washington)</title><addtitle>Anal. Chem</addtitle><description>Exocyclic DNA adducts, including 1,N 2-propano-2′-deoxyguanosine derived from acrolein (AdG) and crotonaldehyde (CdG) and the three lipid peroxidation-related etheno adducts 1,N 6-etheno-2′-deoxyadenosine (εdAdo), 3,N 4-etheno-2′-deoxycytidine (εdCyt), and 1,N 2-etheno-2′-deoxyguanosine (1,N 2-εdGuo), play an important role in cancer formation and they are associated with oxidative-stress-induced DNA damage. Saliva is an easily accessible and available biological fluid and a potential target of noninvasive biomarkers. In this study, a highly sensitive and specific assay based on isotope dilution nanoflow LC–nanospray ionization tandem mass spectrometry (nanoLC–NSI/MS/MS) is developed for simultaneous detection and quantification of these five adducts in human salivary DNA. The levels of AdG, CdG, εdAdo, εdCyd, and 1,N 2-εdGuo, measured in 27 human salivary DNA samples from healthy volunteers, were determined as 104 ± 50, 7.6 ± 12, 99 ± 50, 72 ± 49, 391 ± 198 (mean ± SD) in 108 normal nucleotides, respectively, starting with 25 μg of DNA isolated from an average of 3 mL of saliva. Statistically significant correlations were found between levels of εdAdo and εdCyd (γ = 0.8007, p < 0.0001), between levels of εdAdo and 1,N 2-εdGuo (γ = 0.6778, p = 0.0001), between levels of εdCyd and 1,N 2-εdGuo (γ = 0.5643, p = 0.0022), between levels of AdG and 1,N 2-εdGuo (γ = 0.5756, p = 0.0017), and between levels of AdG and εdAdo (γ = 0.3969, p = 0.0404). Only 5 μg of DNA sample was analyzed for simultaneous quantification of these adducts. The easy accessibility and availability of saliva and the requirement for the small amount of DNA samples make this nanoLC–NSI/MS/MS assay clinically feasible in assessing the possibility of measuring 1,N 2-propano-2′-deoxyguanosine and etheno adducts levels in human salivary DNA as noninvasive biomarkers for DNA damage resulting from oxidative stress and for evaluating their roles in cancer formation and prevention.</description><subject>Analytical chemistry</subject><subject>Body fluids</subject><subject>Chemistry</subject><subject>Chromatographic methods and physical methods associated with chromatography</subject><subject>Chromatography, Liquid</subject><subject>Correlation analysis</subject><subject>DNA Adducts - analysis</subject><subject>DNA Adducts - chemistry</subject><subject>DNA damage</subject><subject>Exact sciences and technology</subject><subject>Humans</subject><subject>Indicator Dilution Techniques</subject><subject>Isotopes</subject><subject>Lipids</subject><subject>Nanotechnology - methods</subject><subject>Other chromatographic methods</subject><subject>Oxidative stress</subject><subject>Reference Values</subject><subject>Salivary Glands - metabolism</subject><subject>Spectrometric and optical methods</subject><subject>Tandem Mass Spectrometry</subject><issn>0003-2700</issn><issn>1520-6882</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpl0c1u1DAQB_AIgei2cOAFkIWEEIeAP5I4Oa62ha60LUJbztGs41BXjp36o5CeeAcehvfhSfC2y1aCky3595-xZrLsBcHvCKbkPQiKSc2L7lE2IyXFeVXX9HE2wxiznHKMD7JD768wJgST6ml2QElT1qzgs-zX5wgmqABB3Ug0N6AnrzyyPTqLOqhRS3Ty3YpJaCXQ8fkczbsuiuCRMug0DmDQGrS6ATfdvW4mtA6wSamlt8GOEh0rHYOyBp2Dsb2239BKXUfVocWlswME-9XBeDn9_vFzC_zoYEJLa9Qt3KUuwHRyQGfgPVqPUoQUksFNz7InPWgvn-_Oo-zLh5OLxWm--vRxuZivcigYDzmj0Ikak5LTgrOyrCmuhehqvmk2PWV10dGmKRkAY-nad5yR5AXrq77oBTTsKHtzX3d09jpKH9pBeSG1BiNt9G2DC0woJzjJV__IKxtdGugWVQWrcFUl9PYeCWe9d7JvR6eGNL2W4Ha7y3a_y2Rf7grGzSC7vfy7vARe7wB4Abp3YITyD67gHLPUee9A-IdP_d_wD2SLtbA</recordid><startdate>20111115</startdate><enddate>20111115</enddate><creator>Chen, Hauh-Jyun Candy</creator><creator>Lin, Wen-Peng</creator><general>American Chemical Society</general><scope>IQODW</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>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7TA</scope><scope>7TB</scope><scope>7TM</scope><scope>7U5</scope><scope>7U7</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20111115</creationdate><title>Quantitative Analysis of Multiple Exocyclic DNA Adducts in Human Salivary DNA by Stable Isotope Dilution Nanoflow Liquid Chromatography–Nanospray Ionization Tandem Mass Spectrometry</title><author>Chen, Hauh-Jyun Candy ; Lin, Wen-Peng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a437t-32adc801572473558208ccd87b9bf2384d29953aa334d2fd731dc8c3f6f4fca93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Analytical chemistry</topic><topic>Body fluids</topic><topic>Chemistry</topic><topic>Chromatographic methods and physical methods associated with chromatography</topic><topic>Chromatography, Liquid</topic><topic>Correlation analysis</topic><topic>DNA Adducts - analysis</topic><topic>DNA Adducts - chemistry</topic><topic>DNA damage</topic><topic>Exact sciences and technology</topic><topic>Humans</topic><topic>Indicator Dilution Techniques</topic><topic>Isotopes</topic><topic>Lipids</topic><topic>Nanotechnology - methods</topic><topic>Other chromatographic methods</topic><topic>Oxidative stress</topic><topic>Reference Values</topic><topic>Salivary Glands - metabolism</topic><topic>Spectrometric and optical methods</topic><topic>Tandem Mass Spectrometry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Hauh-Jyun Candy</creatorcontrib><creatorcontrib>Lin, Wen-Peng</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Analytical chemistry (Washington)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Hauh-Jyun Candy</au><au>Lin, Wen-Peng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Quantitative Analysis of Multiple Exocyclic DNA Adducts in Human Salivary DNA by Stable Isotope Dilution Nanoflow Liquid Chromatography–Nanospray Ionization Tandem Mass Spectrometry</atitle><jtitle>Analytical chemistry (Washington)</jtitle><addtitle>Anal. Chem</addtitle><date>2011-11-15</date><risdate>2011</risdate><volume>83</volume><issue>22</issue><spage>8543</spage><epage>8551</epage><pages>8543-8551</pages><issn>0003-2700</issn><eissn>1520-6882</eissn><coden>ANCHAM</coden><abstract>Exocyclic DNA adducts, including 1,N 2-propano-2′-deoxyguanosine derived from acrolein (AdG) and crotonaldehyde (CdG) and the three lipid peroxidation-related etheno adducts 1,N 6-etheno-2′-deoxyadenosine (εdAdo), 3,N 4-etheno-2′-deoxycytidine (εdCyt), and 1,N 2-etheno-2′-deoxyguanosine (1,N 2-εdGuo), play an important role in cancer formation and they are associated with oxidative-stress-induced DNA damage. Saliva is an easily accessible and available biological fluid and a potential target of noninvasive biomarkers. In this study, a highly sensitive and specific assay based on isotope dilution nanoflow LC–nanospray ionization tandem mass spectrometry (nanoLC–NSI/MS/MS) is developed for simultaneous detection and quantification of these five adducts in human salivary DNA. The levels of AdG, CdG, εdAdo, εdCyd, and 1,N 2-εdGuo, measured in 27 human salivary DNA samples from healthy volunteers, were determined as 104 ± 50, 7.6 ± 12, 99 ± 50, 72 ± 49, 391 ± 198 (mean ± SD) in 108 normal nucleotides, respectively, starting with 25 μg of DNA isolated from an average of 3 mL of saliva. Statistically significant correlations were found between levels of εdAdo and εdCyd (γ = 0.8007, p < 0.0001), between levels of εdAdo and 1,N 2-εdGuo (γ = 0.6778, p = 0.0001), between levels of εdCyd and 1,N 2-εdGuo (γ = 0.5643, p = 0.0022), between levels of AdG and 1,N 2-εdGuo (γ = 0.5756, p = 0.0017), and between levels of AdG and εdAdo (γ = 0.3969, p = 0.0404). Only 5 μg of DNA sample was analyzed for simultaneous quantification of these adducts. The easy accessibility and availability of saliva and the requirement for the small amount of DNA samples make this nanoLC–NSI/MS/MS assay clinically feasible in assessing the possibility of measuring 1,N 2-propano-2′-deoxyguanosine and etheno adducts levels in human salivary DNA as noninvasive biomarkers for DNA damage resulting from oxidative stress and for evaluating their roles in cancer formation and prevention.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>21958347</pmid><doi>10.1021/ac201874d</doi><tpages>9</tpages></addata></record> |
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| subjects | Analytical chemistry Body fluids Chemistry Chromatographic methods and physical methods associated with chromatography Chromatography, Liquid Correlation analysis DNA Adducts - analysis DNA Adducts - chemistry DNA damage Exact sciences and technology Humans Indicator Dilution Techniques Isotopes Lipids Nanotechnology - methods Other chromatographic methods Oxidative stress Reference Values Salivary Glands - metabolism Spectrometric and optical methods Tandem Mass Spectrometry |
| title | Quantitative Analysis of Multiple Exocyclic DNA Adducts in Human Salivary DNA by Stable Isotope Dilution Nanoflow Liquid Chromatography–Nanospray Ionization Tandem Mass Spectrometry |
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