[21] Measuring DNA adducts by gas chromatography-electron capture-mass spectrometry: Trace organic analysis

Giese, Roger W.; Saha, Manasi; Abdel-Baky, Samy; Allam, Kariman

doi:10.1016/s0076-6879(96)71023-6

Cited by 11 publications

(5 citation statements)

References 17 publications

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“…We were unable to detect 5-chlorocytosine in bacteria exposed to activated neutrophils. However, the limit of detection in this analysis was ϳ1 in 10 4 nucleobases, and studies of other DNA oxidation products suggest that the physiologically relevant level will be on the order of 1 in 10 7 -10 8 nucleobases (56). In future studies it will clearly be important to use more sensitive methods to determine whether phagocytes halogenate nucleotides and polymeric nucleic acids of intact bacterial and mammalian cells.…”

Section: Activated Human Neutrophils Employ the Myeloperoxidase-h 2 Omentioning

confidence: 87%

Molecular Chlorine Generated by the Myeloperoxidase-Hydrogen Peroxide-Chloride System of Phagocytes Produces 5-Chlorocytosine in Bacterial RNA

Henderson

Byun

Heinecke

1999

Journal of Biological Chemistry

114

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Myeloperoxidase, a heme enzyme secreted by activated phagocytes, uses H 2 O 2 and Cl؊ to generate the chlorinating intermediate hypochlorous acid (HOCl). This potent cytotoxic oxidant plays a critical role in host defenses against invading pathogens. In this study, we explore the possibility that myeloperoxidase-derived HOCl might oxidize nucleic acids. When we exposed 2-deoxycytidine to the myeloperoxidase-H 2 O 2 -Cl ؊ system, we obtained a single major product that was identified as 5-chloro-2-deoxycytidine using mass spectrometry, high performance liquid chromatography, UV-visible spectroscopy, and NMR spectroscopy. 5-Chloro-2-deoxycytidine production by myeloperoxidase required H 2 O 2 and Cl and H؉ , in the generation of 5-chloro-2-deoxycytidine. Activated human neutrophils were able to generate 5-chloro-2-deoxycytidine. Cellular chlorination was blocked by catalase and heme poisons, consistent with a myeloperoxidase-catalyzed reaction. The myeloperoxidase-H 2 O 2 -Cl ؊ system generated similar levels of 5-chlorocytosine in RNA and DNA in vitro. In striking contrast, only cell-associated RNA acquired detectable levels of 5-chlorocytosine when intact Escherichia coli was exposed to the myeloperoxidase system. This observation suggests that oxidizing intermediates generated by myeloperoxidase selectively target intracellular RNA for chlorination. Collectively, these results indicate that Cl 2 derived from HOCl generates 5-chloro-2-deoxycytidine during the myeloperoxidase-catalyzed oxidation of 2-deoxycytidine. Phagocytic generation of Cl 2 therefore may constitute one mechanism for oxidizing nucleic acids at sites of inflammation.

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Section: Activated Human Neutrophils Employ the Myeloperoxidase-h 2 Omentioning

confidence: 87%

Molecular Chlorine Generated by the Myeloperoxidase-Hydrogen Peroxide-Chloride System of Phagocytes Produces 5-Chlorocytosine in Bacterial RNA

Henderson

Byun

Heinecke

1999

Journal of Biological Chemistry

114

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“…Trace organic analysis [1][2][3] is commonly performed by combining a chromatographic method [4] with mass spectrometry (MS) [5]. Ambient ionization [6][7][8][9][10][11][12][13][14] is a relatively recent approach to MS analysis which avoids chromatography and is characterized by the absence of any requirement for sample preparation.…”

Section: Introductionmentioning

confidence: 99%

Biogenic aldehyde determination by reactive paper spray ionization mass spectrometry

Bag

Hendricks

Reynolds

et al. 2015

Analytica Chimica Acta

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Ionization of aliphatic and aromatic aldehydes is improved by performing simultaneous chemical derivatization using 4-aminophenol to produce charged iminium ions during paper spray ionization.Accelerated reactions occur in the microdroplets generated during the paper spray ionization event for the tested aldehydes (formaldehyde, n-pentanaldehyde, n-nonanaldehyde, n-decanaldehyde, ndodecanaldehyde, benzaldehyde, m-anisaldehyde, and p-hydroxybenzaldehyde). Tandem mass spectrometric analysis of the iminium ions using collision-induced dissociation demonstrated that straight chain aldehydes give a characteristic fragment at m/z 122 (shown to correspond to protonated 4-(methyleneamino)phenol), while the arylaldehydeiminium ions fragment to give a characteristic product ion at m/z 120. These features allow straightforward identification of linear and aromatic aldehydes. Quantitative analysis of n-nonaldehyde using a benchtop mass spectrometer demonstrated a linear response over 3 orders of magnitude from 2.5 ng -5 µg of aldehyde loaded on the filter paper emitter. The limit of detection was determined to be 2.2 ng for this aldehyde. The method had a precision of 22%, relative standard deviation. The experiment was also implemented using a portable ion trap mass spectrometer.3

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“…The major challenge for the detection of DNA adducts in biological samples is that the concentration of adducts in DNA can be very low. A sensitive analytical method is essential to be able to detect low picomolar, or in many situations even femtomolar, amounts of adducts with limited sample availability 4. In addition, the analytical method must be specific enough to confirm the structure of adducts in complex biological matrices.…”

Section: Introductionmentioning

confidence: 99%

Quantitative detection of N⁷‐(2‐hydroxyethyl)guanine adducts in DNA using high‐performance liquid chromatography/electrospray ionization tandem mass spectrometry

Liao

Hung

et al. 2001

J. Mass Spectrom.

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High-performance liquid chromatography (HPLC) was combined with electrospray ionization tandem mass spectrometry (ESI-MS/MS) to develop a sensitive and selective method for the quantitative measurement of N(7)-(2-hydroxyethyl)guanine (N(7)-HEG) adducts in DNA obtained from ethylene oxide-exposed biological samples. Selected reaction monitoring (SRM) was used as the detection mode while the fragmentation product ion at m/z 152 generated from the precursor protonated N(7)-HEG (m/z 196) was monitored. The detection limits for N(7)-HEG were estimated by twofold serial dilution and determined to be 4 fmol in neat standard solution and 16 fmol when a matrix effect is considered. When the mass spectrometer was operated in the selected ion monitoring mode using only the first quadrupole (without MS/MS function), the detection limits increased to 128 fmol and 1 pmol (when matrix effect is considered), respectively. A good linear correlation (R(2) = 0.999) was observed for signal intensities obtained by injecting 16 fmol--33 pmol of N(7)-HEG into the HPLC/ESI-MS/MS system. Hep G2 cells were incubated for 8 h with medium containing various concentrations of ethylene oxide (ranging from 0.05 to 5.0 mM). A dose-response relationship was established, indicating that the adduct formation increases with the exposure level. The method shows potential, although the detection limit needs to be lowered for practical applications, for use in monitoring N(7)-HEG formation in other biological systems.

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[21] Measuring DNA adducts by gas chromatography-electron capture-mass spectrometry: Trace organic analysis

Cited by 11 publications

References 17 publications

Molecular Chlorine Generated by the Myeloperoxidase-Hydrogen Peroxide-Chloride System of Phagocytes Produces 5-Chlorocytosine in Bacterial RNA

Molecular Chlorine Generated by the Myeloperoxidase-Hydrogen Peroxide-Chloride System of Phagocytes Produces 5-Chlorocytosine in Bacterial RNA

Biogenic aldehyde determination by reactive paper spray ionization mass spectrometry

Quantitative detection of N⁷‐(2‐hydroxyethyl)guanine adducts in DNA using high‐performance liquid chromatography/electrospray ionization tandem mass spectrometry

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[21] Measuring DNA adducts by gas chromatography-electron capture-mass spectrometry: Trace organic analysis

Cited by 11 publications

References 17 publications

Molecular Chlorine Generated by the Myeloperoxidase-Hydrogen Peroxide-Chloride System of Phagocytes Produces 5-Chlorocytosine in Bacterial RNA

Molecular Chlorine Generated by the Myeloperoxidase-Hydrogen Peroxide-Chloride System of Phagocytes Produces 5-Chlorocytosine in Bacterial RNA

Biogenic aldehyde determination by reactive paper spray ionization mass spectrometry

Quantitative detection of N7‐(2‐hydroxyethyl)guanine adducts in DNA using high‐performance liquid chromatography/electrospray ionization tandem mass spectrometry

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Quantitative detection of N⁷‐(2‐hydroxyethyl)guanine adducts in DNA using high‐performance liquid chromatography/electrospray ionization tandem mass spectrometry