Detection and Quantification of N-(Deoxyguanosin-8-yl)-4-aminobiphenyl Adducts in Human Pancreas Tissue Using Capillary Liquid Chromatography-Microelectrospray Mass Spectrometry
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- 作者：Elaine M. Ricicki ; John R. Soglia ; Candee Teitel ; Robert Kane ; Fred Kadlubar ; and Paul Vouros
- 刊名：Chemical Research in Toxicology
- 出版年：2005
- 出版时间：April 2005
- 年：2005
- 卷：18
- 期：4
- 页码：692 - 699
- 全文大小：396K
- 年卷期：v.18,no.4(April 2005)
- ISSN：1520-5010
文摘
Cigarette smoking has been associated with various cancers including bladder and pancreas.4-Aminobiphenyl has been isolated as a constituent of cigarette smoke and has been establishedas a carcinogen in various animal models and humans. In rodents and humans, 4-aminobiphenyl is N-hydroxylated and forms adducts to DNA, the predominant one being N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP). In this study, we report a micro-electrospraymass spectrometric (
r.gif">ESI-MS) isotope dilution method for the detection and quantification ofdG-C8-ABP in human pancreatic tissue. A reverse phase capillary column (320 r.gif">m ID) wasconnected to a triple quadrupole mass spectrometer via a commercially available micro-ESIsource. The system was operated in the selected reaction monitoring mode transmitting the[M + H]+ 
rarr.gif"> [M + H - 116]+ transitions for both the analyte and the isotopically labeled internalstandard. Twelve human pancreas samples were analyzed, where six were current smokers(three male and three female) and six were considered nonsmokers (three female and threemale). Of the samples analyzed, six showed dG-C8-ABP levels above the limit of quantificationfor the method, five were considered to have levels that were undetectable, and one wasdiscarded due to inconsistent internal standard signal. The age of the human subjects rangedfrom 17 to 63, and, in samples where adduct was present, levels ranged anywhere from 1 to60/108 nucleotides. Although no correlation between smoking preference, age, or gender wasproven with this particular sample pool, this report demonstrates that capillary LC-r.gif">ESI-MScan provide a sensitive and definitive method for DNA adduct analysis in human tissue.
r.gif">ESI-MS) isotope dilution method for the detection and quantification ofdG-C8-ABP in human pancreatic tissue. A reverse phase capillary column (320 r.gif">m ID) wasconnected to a triple quadrupole mass spectrometer via a commercially available micro-ESIsource. The system was operated in the selected reaction monitoring mode transmitting the[M + H]+ rarr.gif"> [M + H - 116]+ transitions for both the analyte and the isotopically labeled internalstandard. Twelve human pancreas samples were analyzed, where six were current smokers(three male and three female) and six were considered nonsmokers (three female and threemale). Of the samples analyzed, six showed dG-C8-ABP levels above the limit of quantificationfor the method, five were considered to have levels that were undetectable, and one wasdiscarded due to inconsistent internal standard signal. The age of the human subjects rangedfrom 17 to 63, and, in samples where adduct was present, levels ranged anywhere from 1 to60/108 nucleotides. Although no correlation between smoking preference, age, or gender wasproven with this particular sample pool, this report demonstrates that capillary LC-r.gif">ESI-MScan provide a sensitive and definitive method for DNA adduct analysis in human tissue.