Mass Spectrometry of Structurally Modified DNA

Tretyakova, Natalia; Villalta, Peter W.; Kotapati, Srikanth

doi:10.1021/cr300391r

Cited by 121 publications

(153 citation statements)

References 350 publications

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“…In consequence, such MS systems are particularly well suited for DNA adductomics [12,40]. As it is our goal to implement the described method in the search for DNA • An UHPLC-HRMS/MS method using Quadrupole-Orbitrap technology was developed for the detection of diet-related DNA adducts.…”

Section: Resultsmentioning

confidence: 99%

High resolution mass spectrometry based profiling of diet-related deoxyribonucleic acid adducts

Hemeryck

Decloedt

Bussche

et al. 2015

Analytica Chimica Acta

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Exposure of DNA to endo- and exogenous DNA binding chemicals can result in the formation of DNA adducts and is believed to be the first step in chemically induced carcinogenesis. DNA adductomics is a relatively new field of research which studies the formation of known and unknown DNA adducts in DNA due to exposure to genotoxic chemicals. In this study, a new UHPLC-HRMS(/MS)-based DNA adduct detection method was developed and validated. Four targeted DNA adducts, which all have been linked to dietary genotoxicity, were included in the described method; O(6)-methylguanine (O(6)-MeG), O(6)-carboxymethylguanine (O(6)-CMG), pyrimidopurinone (M1G) and methylhydroxypropanoguanine (CroG). As a supplementary tool for DNA adductomics, a DNA adduct database, which currently contains 123 different diet-related DNA adducts, was constructed. By means of the newly developed method and database, all 4 targeted DNA adducts and 32 untargeted DNA adducts could be detected in different DNA samples. The obtained results clearly demonstrate the merit of the described method for both targeted and untargeted DNA adduct detection in vitro and in vivo, whilst the diet-related DNA adduct database can distinctly facilitate data interpretation.

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Section: Resultsmentioning

confidence: 99%

High resolution mass spectrometry based profiling of diet-related deoxyribonucleic acid adducts

Hemeryck

Decloedt

Bussche

et al. 2015

Analytica Chimica Acta

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“…61,62 By coupling of a TOF-MS to a quadrupole, the resulting hybrid instrument can also be easily employed for both identification and quantitation purposes since accurate mass measurements are important for confident compound identification and can also eliminate spectral noise due to matrix interferences. 40 Esmans, Van den Driessche and colleagues published research 63,64 on the use of a QTOF instrument for DNA adduct screening and characterization. Unfortunately, and to the best of our knowledge, both the use of the QTOF (quadrupole coupled to TOF) and MALDI-TOF/TOF instruments for DNA adductome mapping has not been explored further which may be due to the lack of available instrumentation in appropriate research laboratories as tandem MS instrumentation has been favoured in recent years.…”

Section: Time Of Flight High Resolution Mass Spectrometrymentioning

confidence: 99%

“…The orbitrap is often coupled to an ion trap instrument (early on) or a quadrupole (later on), but can also be used as a standalone instrument. 40 Recently, Balbo et al developed a high resolution DD-CNL-MS 3 method for DNA adductomics purposes, using a linear ion trap-orbitrap system. 32 Within the described application, the orbitrap …”

Section: Orbitrap High Resolution Mass Spectrometrymentioning

confidence: 99%

“…40 transition) upon fragmentation; a distinctive feature of nucleoside DNA adducts that has been commonly exploited for DNA adductomic research by means of both triple quads and ion traps. 33,43 Employment of the neutral loss of 2'-deoxyribose by nucleosides, and the potentially characteristic loss of protonated bases (as reported by Inagaki and co-workers 35 ) during DNA adduct fragmentation, could prove to be very rewarding as it allows analysts to focus their attention on the detection of potential DNA adduct biomarkers exclusively by ignoring all non-DNA adduct originating ions and molecules.…”

Section: Perspectives For Mass Spectrometry-based Dna Adductome Mappimentioning

confidence: 99%

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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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“…Theses biomarkers include tumor-specific mutations, methylated DNA fragments, and DNA adducts [1,2]. Identification of DNA adducts is highly promising area of research and development, because the chemical structures of adducts differ significantly from the mutated or methylated DNA.…”

Section: Introductionmentioning

confidence: 99%

Application of UPLC- ESI-q-TOF analysis for screening of the carcinogen-modified DNA-adducts in the circulation DNA of patients with lung cancer

Dementeva¹,

Kokova²,

Ponamoreva³

et al. 2016

AIP Conference Proceedings

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Abstract. In this paper we have presented the development of a new approach to screening a carcinogen associated DNA adducts. As starting-material circulating DNA from blood of patients with a diagnosis of lung cancer was used. To obtain DNA adducts DNA of 100 patients and 100 healthy volunteers was hydrolyzed with 0.1 M hydrochloric acid under heating and then neutralized. The LC-MS analysis was performed on a UPLC-ESI-q-TOF mass spectrometry system with using C-18 column. Mass spectra were recorded in positive mode with 50-1000 m/z range. Simultaneously 7 DNA adducts were identified by using the approach described in this article.

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Mass Spectrometry of Structurally Modified DNA

Cited by 121 publications

References 350 publications

High resolution mass spectrometry based profiling of diet-related deoxyribonucleic acid adducts

High resolution mass spectrometry based profiling of diet-related deoxyribonucleic acid adducts

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

Application of UPLC- ESI-q-TOF analysis for screening of the carcinogen-modified DNA-adducts in the circulation DNA of patients with lung cancer

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