Development of a Nanoscale Liquid Chromatography/Electrospray Mass Spectrometry Methodology for the Detection and Identification of DNA Adducts

Vanhoutte, Koen; Dongen, Walter Van; Hoes, I.; Lemière, Filip; Esmans, Eddy L.; Onckelen, Harry Van; Eeckhout, E. Van den; Soest, and R. E. J. van; Hudson, Andrew J.

doi:10.1021/ac970121q

Cited by 90 publications

(68 citation statements)

References 19 publications

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“…The extent of the development of LC-MS for DNA adduct detection can be gauged by the increasing number of publications where DNA adducts have been determined in human tissues and urine (92,121,131,132,173,174,180,(183)(184)(185)(186)(187). In terms of future developments for increasing the sensitivity of LC-MS, the introduction of capillary and nano capillary LC (to replace the normally employed narrow bore and microbore LC) coupled to micro-or nanoelectrospray ionization-MS has the potential to increase detection limits and sensitivity of DNA adduct analysis (188)(189)(190). Vanhoutte et al observed an improvement in sensitivity by a factor of 3300 for the detection of 2 0 -deoxyguanosine 5 0 -monophosphate adducts of bisphenol A diglycidyl ether using nano capillary LC when compared with conventional LC (189).…”

Section: Analytical Developmentsmentioning

confidence: 99%

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

2005

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Section: Analytical Developmentsmentioning

confidence: 99%

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

2005

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“…The coupling of a miniaturized 2-DLC system to tandem mass spectrometry is a powerful approach enabling the analysis of low quantities of DNA-adducts present in a matrix of mainly unmodified 2'-deoxynucleosides [33,[42][43][44][45][46][47][48][49].…”

Section: Lc-ms Analysis Of Standard Dna Adductsmentioning

confidence: 99%

Detection of estrogen DNA-adducts in human breast tumor tissue and healthy tissue by combined nano LC-nano ES tandem mass spectrometry

Embrechts

Lemière

Dongen

et al. 2003

J. Am. Soc. Mass Spectrom.

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For the first time estrogen DNA-adducts were identified in DNA human breast tumor tissue using nano-LC coupled to nano-Electrospray Tandem Mass Spectrometry. Normal breast tissue was analyzed analogously. The data obtained in the five breast tumor and five adjacent normal tissue samples were compared qualitatively, but no straightforward difference was observed. Prior to LC-MS analysis the DNA was enzymatically hydrolyzed to a nucleoside pool. The DNA-hydrolysates were directly injected onto a column switching system developed for on-line sample clean-up and subsequent analysis of the DNA-adducts. In four patients using Premarin, DNA-adducts of 4-hydroxy-equilenin (4OHEN) were detected. All except three samples contained DNA-adducts from 4-hydroxy-estradiol or 4-hydroxy-estrone. Also DNA isolated from eight alcohol fixed and paraffin embedded breast tumor tissue showed the presence of different estrogen DNA-adducts. Worthwhile mentioning is the presence of adducts responding to m/z 570 Ͼ m/z 454 transition. This is a well-known SRM-transition indicative for the presence of the 2'-deoxyguanosine (dGuo) adduct of Benzo H ormone treatment is widespread for women of all ages. In the United States, for instance, 30% of post-menopausal women use hormone eeplacement therapy (HRT) [1], e.g., Premarin. Studies in which the development of breast and endometrial cancer was associated with estrogen therapy [2][3][4][5][6] were supported by a more recent follow-up study in which it was demonstrated that post-menopausal women have an increased risk of breast cancer when using estrogens, especially in combination with progestin [7]. In animals, too, a relationship between the administration of estrogens and the development of cancer was shown [8].The carcinogenic properties of estrogens are explained by direct stimulation of cell proliferation via estrogen receptor mediated mechanisms [9,10] and by mechanisms based on metabolic activation [11][12][13][14], leading to DNA damage such as oxidative damage [15][16][17][18] and the formation of DNA-adducts [19 -28], which can cause mutations and induce cancer [29].The latter pathways are the result of metabolic activation of estrogens by the cytochrome P-450 system leading to 2-and 4-hydroxy derivatives. The 2-hydroxy estrogens are excreted in the urine as a result of their fast transformation to water-soluble compounds [13,14]. The 4-hydroxy form, however, has a longer half-life

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“…For these purposes, several analytical techniques are used, such as high-performance chromatography (HPLC) in combination with fluorescence detection, 1,2 32 P post-labeling 3 -5 and gas chromatography/mass spectrometry (GC/MS). 6,7 Recently, it has been demonstrated by us and others that electrospray mass spectrometry (ES-MS) and electrospray tandem mass spectrometry (ES-MS/MS) if coupled to capillary 8 or nano-HPLC 9 or capillary zone electrophoresis (CZE) 10 offers a unique analytical tool capable of analyzing DNA adducts at the nucleoside or even the nucleotide level. Furthermore, it should be emphasized that ES-MS/MS provides important structural information.…”

Section: Introductionmentioning

confidence: 99%

“…After filtration (0.2 µm) the aqueous solutions was used for analysis. 9 Under these conditions, the adducts were retained. Unmodified nucleosides were washed from the precolumn after 1 min, after which the adducts were backflushed to the analytical column at a flow-rate of 5 µl min 1 starting with an isocratic development using MeOH/0.01 M NH 4 OAc (35 : 65) for 10 min followed by a linear gradient to MeOH/0.01 M NH 4 OAc (90 : 10) over 5 min.…”

mentioning

confidence: 99%

Differentiation between isomeric phenylglycidyl ether adducts of 2′-deoxyguanosine and 2′-deoxyguanosine-5′-monophosphate using liquid chromatography/electrospray tandem mass spectrometry

Lemière¹,

Vanhoutte²,

Jonckers³

et al. 1999

J. Mass Spectrom.

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The reaction between phenylglycidyl ether and 2′‐deoxyguanosine or 2′‐deoxyguanosine‐5′‐monophosphate yields a variety of different nucleoside and nucleotide adducts. The corresponding mixtures were analyzed by liquid chromatography/electrospray tandem mass spectrometry and the product ion spectra of the different isomers are discussed using the correct cone voltage and collision energy. The latter were selected by looking at the energy‐resolved spectra. From these data the formation of N7 and N2 isomers was proposed. However, detailed NMR analysis of the latter proved this isomer to be the N1‐alkylated adduct. The reaction between phenylglycidyl ether and 2′‐deoxyguanosine or 2′‐deoxyguanosine‐5′‐monophosphate yields a variety of different nucleoside and nucleotide adducts. The corresponding mixtures were analyzed by liquid chromatography/electrospray tandem mass spectrometry and the product ion spectra of the different isomers are discussed using the correct cone voltage and collision energy. The latter were selected by looking at the energy‐resolved spectra. From these data the formation of N7 and N2 isomers was proposed. However, detailed NMR analysis of the latter proved this isomer to be the N1‐alkylated adduct. 2′‐Deoxyguanosine‐5′‐monophosphate was alkylated by phenylglycidyl ether at the 5′‐phosphate position. If the nucleotide base moiety was alkylated, the corresponding tandem mass spectrometric data strongly suggested alkylation of N7. In the case of bis‐PGE–dGMP adduct, evidence was found for simultaneous 5′‐phosphate and N7‐alkylation.2′‐Deoxyguanosine‐5′‐monophosphate was alkylated by phenylglycidyl ether at the 5′‐phosphate position. If the nucleotide base moiety was alkylated, the corresponding tandem mass spectrometric data strongly suggested alkylation of N7. In the case of bis‐PGE–dGMP adduct, evidence was found for simultaneous 5′‐phosphate and N7‐alkylation. Copyright © 1999 John Wiley & Sons, Ltd.

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Development of a Nanoscale Liquid Chromatography/Electrospray Mass Spectrometry Methodology for the Detection and Identification of DNA Adducts

Cited by 90 publications

References 19 publications

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

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

Detection of estrogen DNA-adducts in human breast tumor tissue and healthy tissue by combined nano LC-nano ES tandem mass spectrometry

Differentiation between isomeric phenylglycidyl ether adducts of 2′-deoxyguanosine and 2′-deoxyguanosine-5′-monophosphate using liquid chromatography/electrospray tandem mass spectrometry

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