Overview of Recent Developments in the Mass Spectrometry of Nucleic Acid and Constituents

Banoub, Joseph; Miller-Banoub, Judith; Jahouh, Farid; Joly, Nicolas; Martin, Patrick

doi:10.1201/9781420044034-c1

Cited by 4 publications

(10 citation statements)

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“…26–31 Therefore, analytical methods used for quantification of carcinogen-DNA adducts must be ultra-sensitive, accurate, and specific, making it possible to quantify low abundance DNA lesions in the presence of a large molar excess of normal nucleosides. 22 32 P-postlabeling involves thin layer chromatography or HPLC separation of radiolabeled nucleotides.…”

Section: Introductionmentioning

confidence: 99%

“…Mass spectrometry using stable isotope labeled internal standards (isotope dilution HPLC-ESI-MS-MS or IDMS) is considered a golden standard for DNA adduct analysis because it provides structural information and due to its high specificity, sensitivity, and accurate quantification. 22,30,31 Several comprehensive reviews have been published over the years that discuss the use of isotope dilution mass spectrometry in DNA adduct analysis. 27,30−33 The present review is focused on the recent developments in isotope dilution HPLC-ESI-MS/ MS and provides some up-to-date examples of mass spectrometry-based detection of DNA adducts in biological samples.…”

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confidence: 99%

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Quantitation of DNA Adducts by Stable Isotope Dilution Mass Spectrometry

Tretyakova

Goggin

Sangaraju

et al. 2012

Chem. Res. Toxicol.

107

125

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Exposure to endogenous and exogenous chemicals can lead to the formation of structurally modified DNA bases (DNA adducts). If not repaired, these nucleobase lesions can cause polymerase errors during DNA replication, leading to heritable mutations and potentially contributing to the development of cancer. Because of their critical role in cancer initiation, DNA adducts represent mechanism-based biomarkers of carcinogen exposure, and their quantitation is particularly useful for cancer risk assessment. DNA adducts are also valuable in mechanistic studies linking tumorigenic effects of environmental and industrial carcinogens to specific electrophilic species generated from their metabolism. While multiple experimental methodologies have been developed for DNA adduct analysis in biological samples, including immunoassay, HPLC, and 32P-postlabeling, isotope dilution high performance liquid chromatography–electrospray ionization–tandem mass spectrometry (HPLC-ESI-MS/MS) generally has superior selectivity, sensitivity, accuracy, and reproducibility. As typical DNA adduct concentrations in biological samples are between 0.01–10 adducts per 108 normal nucleotides, ultrasensitive HPLC-ESI-MS/MS methodologies are required for their analysis. Recent developments in analytical separations and biological mass spectrometry, especially nanoflow HPLC, nanospray ionization MS, chip-MS, and high resolution MS, have pushed the limits of analytical HPLC-ESI-MS/MS methodologies for DNA adducts, allowing researchers to accurately measure their concentrations in biological samples from patients treated with DNA alkylating drugs and in populations exposed to carcinogens from urban air, drinking water, cooked food, alcohol, and cigarette smoke.

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Quantitation of DNA Adducts by Stable Isotope Dilution Mass Spectrometry

Tretyakova

Goggin

Sangaraju

et al. 2012

Chem. Res. Toxicol.

107

125

View full text Add to dashboard Cite

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“…The MALDI technique is typically combined with a time-of-flight (TOF) analyzer; however, the application of MALDI-TOF MS is limited to short oligonucleotides (~25 nucleotides (nt)) owing to the subsequent fragmentation, adduct formation and low ionization efficiency 1,2 . In contrast, ESI is applicable to longer oligonucleotides (>100 nt), but many charge states of multiple charged ions ( [M−nH] n− ) are produced simultaneously from biomacromolecules and, therefore, the mass of the analyte can exceed the upper limit of the m/z range of the spectrometer.…”

Section: Introductionmentioning

confidence: 99%

“…In the context of ESI-MS, dissociation of a DNA duplex, purification and desalting are required for direct measurement to avoid the failure of ionization due to ion suppression and adduct formation 2,[10][11][12][13][14] . These procedures are troublesome, however, fully automated analytical systems have been developed commercially involving polymerase chain reaction (PCR), sample preparation and ESI-MS for the detection of pathogens [15][16][17][18][19][20] .…”

Section: Introductionmentioning

confidence: 99%

“…Mass spectrometry (MS) is an accepted technology for rapid and reliable identification of nucleic acids, matrix-assisted laser desorption/ ionization (MALDI) and electrospray ionization (ESI) being used for ionization 1,2 . The MALDI technique is typically combined with a time-of-flight (TOF) analyzer; however, the application of MALDI-TOF MS is limited to short oligonucleotides (~25 nucleotides (nt)) owing to the subsequent fragmentation, adduct formation and low ionization efficiency 1,2 .…”

Section: Introductionmentioning

confidence: 99%

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Improved Polymerase Chain Reaction-restriction Fragment Length Polymorphism Genotyping of Toxic Pufferfish by Liquid Chromatography/Mass Spectrometry

Miyaguchi

2016

JoVE

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An improved version of a polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method for genotyping toxic pufferfish species by liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) is described. DNA extraction is carried out using a silica membrane-based DNA extraction kit. After the PCR amplification using a detergent-free PCR buffer, restriction enzymes are added to the solution without purifying the reaction solution. A reverse-phase silica monolith column and a Fourier transform high resolution mass spectrometer having a modified Kingdon trap analyzer are employed for separation and detection, respectively. The mobile phase, consisting of 400 mM 1,1,1,3,3,3-hexafluoro-2-propanol, 15 mM triethylamine (pH 7.9) and methanol, is delivered at a flow rate of 0.4 ml/min. The cycle time for LC/ESI-MS analysis is 8 min including equilibration of the column. Deconvolution software having an isotope distribution model of the oligonucleotide is used to calculate the corresponding monoisotopic mass from the mass spectrum. For analysis of oligonucleotides (range 26-79 nucleotides), mass accuracy was 0.62 ± 0.74 ppm (n = 280) and excellent accuracy and precision were sustained for 180 hr without use of a lock mass standard.

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Purines, Pyrimidines, and Nucleotides

Aaron

Aaron²

2014

Reference Module in Chemistry, Molecular Sciences and Chemical Engineering

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Overview of Recent Developments in the Mass Spectrometry of Nucleic Acid and Constituents

Cited by 4 publications

References 0 publications

Quantitation of DNA Adducts by Stable Isotope Dilution Mass Spectrometry

Quantitation of DNA Adducts by Stable Isotope Dilution Mass Spectrometry

Improved Polymerase Chain Reaction-restriction Fragment Length Polymorphism Genotyping of Toxic Pufferfish by Liquid Chromatography/Mass Spectrometry

Purines, Pyrimidines, and Nucleotides

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