Application of capillary liquid chromatography coupled with tandem mass spectrometric methods to the rapid screening of adducts formed by the reaction of N-acetoxy-N-acetyl-2-aminofluorene with calf DNA

Wolf, Susan M.; Vouros, Paul

doi:10.1021/tx00037a013

Cited by 54 publications

(72 citation statements)

References 21 publications

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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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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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“…Lakshmi and coworkers [28,29] utilized an ESI tandem mass spectral method for analysis of N-acetylaminobenzidine guanine adducts to confirm the identity of adducts detected through P32-postlabelling but not for quantitative analysis. Wolf and Vouros [30,31] developed a capillary electrophoresis tandem mass spectrometric method for quantification of N-acetyl aminofluorene N2-and C8-guanine adducts formed in vitro with calf thymus DNA. They reported detection limits for these adducts in the range of 50 fmole on-column.…”

Section: Spike and Recovery Studiesmentioning

confidence: 99%

Development of an isotope dilution liquid chromatography/tandem mass spectrometry detection method for DNA adducts of selected aromatic amines

Means

Olsen

Schoffers

2003

J. Am. Soc. Mass Spectrom.

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Polycyclic aromatic amines (arylamines) are a class of chemical carcinogens that are prevalent in environmental and industrial settings. They are metabolically activated to covalently bond to DNA, forming mutagenic adducts. In order to study the mechanisms of their toxicity, sensitive and selective quantitative LC/MS/MS detection methods were developed to measure the N-(adenin-8-yl)-benzidine adduct and N-(adenin-8-yl)-2-aminofluorene in total DNA extract samples. A novel synthetic method using a palladium catalyst was previously developed to prepare authentic and deuterated arylamine-adenine adducts to serve as standards. These standards were then used to develop an HPLC electrospray ionization tandem mass spectrometry, isotope dilution method. Sample detection limits in DNA samples were 22 pg on-column and 51 pg on-column for the N-(adenin-8-yl)-benzidine-and N-(adenin-8-yl)-2-aminofluorene-adenine adducts, respectively. This method has applications for the study of DNA adduct formation as a biological marker of exposure to carcinogens and for environmental and workplace monitoring of these aromatic amines. (J Am Soc Mass

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“…The identity of the protons was confirmed by their coupling patterns in both the 1 H spectrum and the COSY spectrum. 13 C NMR. The 13 C NMR spectra were recorded and the signals were identified (Table 3) using their chemical shifts and the correlation with the protons in the HETCOR and long-range HETCOR experiments (see below).…”

Section: Nmr Study Of the Pge-dguo Adductsmentioning

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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Application of capillary liquid chromatography coupled with tandem mass spectrometric methods to the rapid screening of adducts formed by the reaction of N-acetoxy-N-acetyl-2-aminofluorene with calf DNA

Cited by 54 publications

References 21 publications

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

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

Development of an isotope dilution liquid chromatography/tandem mass spectrometry detection method for DNA adducts of selected aromatic amines

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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