Liquid chromatography-electrospray ionization-mass spectrometry: the future of DNA adduct detection

Singh, Rajinder; Farmer, Peter B.

doi:10.1093/carcin/bgi260

Cited by 203 publications

(216 citation statements)

References 208 publications

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“…A number of methods have been developed for detection of BPDE-DNA adducts, including capillary electrophoresis (CE)-laserinduced fluorescence (LIF) [13][14][15][16], accelerator mass spectrometry [17,18], liquid chromatography or capillary electrophoresis-mass spectrometry [19][20][21][22][23][24][25][26], and 32 P-postlabelling [27]. However, only few methods demonstrate the capability of resolving the stereoisomers of BPDE-DNA adducts.…”

Section: Introductionmentioning

confidence: 99%

“…Because of the improved detection selectivity, it takes shorter time (20-50 min) for the stereoslective separation [21,22,30]. Due to large sample consumption (30-300 g DNA), the LC-MS based methods are often used for identification of new DNA damage and analysis of DNA adducts from cultured cells or animal tissues rather than human biomonitoring [19,31,32].…”

Section: Introductionmentioning

confidence: 99%

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Ultra-performance liquid chromatography–tandem mass spectrometry for rapid and highly sensitive analysis of stereoisomers of benzo[a]pyrene diol epoxide–DNA adducts

Feng

Wang

Huang

et al. 2009

Journal of Chromatography B

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ultra-performance liquid chromatography–tandem mass spectrometry for rapid and highly sensitive analysis of stereoisomers of benzo[a]pyrene diol epoxide–DNA adducts

Feng

Wang

Huang

et al. 2009

Journal of Chromatography B

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“…[12][13][14] More than a decade ago Koc et al stated that the only disadvantage of MS in the field of DNA adduct analysis, was its sensitivity. 28 Over the years, sensitivity has continued to improve 6,14 as different research groups have focused on optimization of DNA adduct detection methods with MS [30][31][32][33][34][35][36][37] , including research into non-manual data mining and sequencing to locate DNA adduction sites. 38,39 Due to ongoing technical advancements and the use of stable isotope labeled internal standards, MS currently offers a reliable tool to measure low DNA adduct levels with the highest specificity.…”

Section: Mass Spectrometry As the Methods Of Choice For Dna Adductomicsmentioning

confidence: 99%

“…12,13 The characteristic advantages of MS, currently recognized as the gold standard for DNA adduct detection, have been reviewed and argued in the past. 6,12,14 In this paper, we further explore the potential of DNA adductomics studies to map the DNA adductome. In light of this, the tools at hand and several important aspects of DNA adductomic studies, including the issue of DNA adduct and internal standard stability, sample preparation, analysis of target vs. surrogate tissue, method validation and study design are discussed comprehensively.…”

Section: Introductionmentioning

confidence: 99%

Mass Spectrometric Mapping of the DNA Adductome as a Means to Study Genotoxin Exposure, Metabolism, and Effect

2016

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Covalent binding of endo-or exogenous chemicals to DNA results in the formation of DNA adducts which are reflective of exposure of the human body to DNA-damaging molecules and their metabolic pathways. The study of DNA adduct types and levels in human tissue therefore offers an interesting tool in several fields of research, including toxicology and cancer epidemiology. Over the years, a range of techniques and methods have been developed to study the formation of endo-and exogenous DNA adducts. However, for the simultaneous detection, identification and quantification of both known and unknown DNA adducts, mass spectrometry (MS) is deemed to be the most promising technique. In this perspective, we focus on the analysis of multiple DNA adducts within a sample with the emphasis on untargeted analysis. The advantageous use of MS methodologies for DNA adductome mapping is discussed comprehensively with relevant field examples. In addition, several aspects of study design, sample pretreatment and analysis are addressed as these factors significantly affect the reliability of DNA adductomics studies.

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“…32 P-Postlabelling has been the most widely used method for the detection of PhIP-DNA adducts in animal and human tissues offering the advantage that only small amounts of DNA are required for analysis. The development of electrospray ionization (ESI) has permitted the coupling of liquid chromatography (LC) to mass spectrometry (MS), which has been used for the detection of numerous DNA adducts [26]. LC-mass spectrometry has made sufficient gains in sensitivity for the detection of DNA adducts resulting in it being a viable alternative to other detection methods such as 32 P-postlabelling and immunoassays, to provide more accurate and precise results through the use of stable isotope internal standards [27,28].…”

Section: Introductionmentioning

confidence: 99%

Detection and quantitation of N-(deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine adducts in DNA using online column-switching liquid chromatography tandem mass spectrometry

Singh

Arlt

Henderson

et al. 2010

Journal of Chromatography B

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The heterocyclic aromatic amine, 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) is formed by the grilled cooking of certain foods such as meats, poultry and fish. PhIP has been shown to induce tumours in the colon, prostate and mammary glands of rats and is regarded as a potential human dietary carcinogen. PhIP is metabolically activated via cytochrome P450 mediated oxidation to an N-hydroxylamino-PhIP intermediate that is subsequently converted to an ester by N-acetyltransferases or sulfotransferases and undergoes heterolytic cleavage to produce a PhIP-nitrenium ion, which reacts with DNA to form the N-(deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP-C8-dG) adduct. Thus far, the detection and quantification of PhIP-DNA adducts has relied to a large extent on 32 P-postlabelling methodologies. In order to expand the array of available techniques for the detection and improved quantification of PhIP-C8-dG adducts in DNA we have developed an online column-switching liquid chromatography (LC)-electrospray ionization (ESI)-tandem mass spectrometry (MS/MS) selected reaction monitoring (SRM) method incorporating an isotopically [ 13 C 10 ]-labelled PhIP-C8-dG internal standard for the analysis of DNA enzymatically hydrolysed to 2′-deoxynucleosides. A dose-dependent increase was observed for PhIP-C8-dG adducts when salmon testis DNA was reacted with N-acetoxy-PhIP. Analysis of DNA samples isolated from colon tissue of mice treated by oral gavage daily for 5 days with 50 mg/kg body weight of PhIP resulted in the detection of an average level of 14.8 ± 3.7 PhIP-C8-dG adducts per 10 6 2′-deoxynucleosides. The method required 50 μg of hydrolysed animal DNA on column and the limit of detection for PhIP-C8-dG was 2.5 fmol (1.5 PhIP-C8-dG adducts per 10 8 2′-deoxynucleosides). In summary, the LC-ESI-MS/MS SRM method provides for the rapid automation of the sample clean up and a reduction in matrix components that would otherwise interfere with the mass spectrometric analysis, with sufficient sensitivity and precision to analyse DNA adducts in animals exposed to PhIP.

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Liquid chromatography-electrospray ionization-mass spectrometry: the future of DNA adduct detection

Cited by 203 publications

References 208 publications

Ultra-performance liquid chromatography–tandem mass spectrometry for rapid and highly sensitive analysis of stereoisomers of benzo[a]pyrene diol epoxide–DNA adducts

Ultra-performance liquid chromatography–tandem mass spectrometry for rapid and highly sensitive analysis of stereoisomers of benzo[a]pyrene diol epoxide–DNA adducts

Mass Spectrometric Mapping of the DNA Adductome as a Means to Study Genotoxin Exposure, Metabolism, and Effect

Detection and quantitation of N-(deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine adducts in DNA using online column-switching liquid chromatography tandem mass spectrometry

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