| Column switching HPLC-ESI(+)-MS/MS methods for quantitative analysis of exocyclic dA adducts in the DNA of laboratory animals exposed to 1,3-butadiene. | |
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MedLine Citation:
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PMID: 20229982 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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1,3-Butadiene (BD) is an important industrial and environmental chemical classified as a human carcinogen on the basis of epidemiological evidence for an increased incidence of leukemia in workers occupationally exposed to BD and its carcinogenicity in laboratory rats and mice. BD is metabolically activated to epoxide intermediates that can react with nucleophilic sites of cellular biomolecules. Among these, 1,2,3,4-diepoxybutane (DEB) is considered the ultimate carcinogenic species of BD due to its potent genotoxicity and mutagenicity attributed to the ability to form DNA-DNA cross-links and exocyclic nucleoside adducts. DEB mutagenesis studies suggest that adducts formed at adenine bases may be critically important, as DEB induces large numbers of A --> T transversion mutations. We have recently identified two regioisomeric exocyclic DEB-dA adducts, 1,N(6)-(2-hydroxy-3-hydroxymethylpropan-1,3-diyl)-2'-deoxyadenosine (1,N(6)-gamma-HMHP-dA) and 1,N(6)-(1-hydroxymethyl-2-hydroxypropan-1,3-diyl)-2'-deoxyadenosine (1,N(6)-alpha-HMHP-dA) ( Seneviratne et al. ( ( 2010 ) Chem. Res. Toxicol. 23 , 118 - 133 ), which were detected in DEB-treated calf thymus DNA and in tissues of BD-exposed laboratory animals. In the present work, we describe a column switching HPLC-ESI(+)-MS/MS methodology for the quantitative analysis of 1,N(6)-HMHP-dA isomers in the DNA of laboratory mice exposed to BD by inhalation. On the basis of their exocyclic structure, which prevents normal Watson-Crick base pairing, these adducts could be responsible for mutations at the A:T base pairs observed following exposure to DEB. |
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Authors:
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Melissa Goggin; Uthpala Seneviratne; James A Swenberg; Vernon E Walker; Natalia Tretyakova |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Chemical research in toxicology Volume: 23 ISSN: 1520-5010 ISO Abbreviation: Chem. Res. Toxicol. Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-04-19 Completed Date: 2010-07-27 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 8807448 Medline TA: Chem Res Toxicol Country: United States |
Other Details:
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Languages: eng Pagination: 808-12 Citation Subset: IM |
Affiliation:
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Department of Medicinal Chemistry and the Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenine
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metabolism Animals Butadienes / chemistry*, toxicity Carcinogens / chemistry*, toxicity Chromatography, High Pressure Liquid / methods* DNA / metabolism DNA Adducts / analysis* Deoxyadenosines / analysis*, chemistry Epoxy Compounds / chemistry, toxicity Inhalation Mice Rats Spectrometry, Mass, Electrospray Ionization / methods* |
| Grant Support | |
ID/Acronym/Agency:
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CA100670/CA/NCI NIH HHS; ES 12689/ES/NIEHS NIH HHS; R01 CA100670-04/CA/NCI NIH HHS; R01 CA100670-05A2/CA/NCI NIH HHS; R01 CA100670-06/CA/NCI NIH HHS; R01 ES012689-05S2/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/1,N6-(1-hydroxymethyl-2-hydroxypropan-1,3-diyl)-2'-deoxyadenosine; 0/1,N6-(2-hydroxy-3-hydroxymethylpropan-1,3-diyl)-2'-deoxyadenosine; 0/Butadienes; 0/Carcinogens; 0/DNA Adducts; 0/Deoxyadenosines; 0/Epoxy Compounds; 106-99-0/1,3-butadiene; 1464-53-5/erythritol anhydride; 73-24-5/Adenine; 9007-49-2/DNA |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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