The Future of DNA Adductomic Analysis

Villalta, Peter W.; Balbo, Silvia

doi:10.3390/ijms18091870

Cited by 55 publications

(67 citation statements)

References 68 publications

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“…LC-MS/MS has become the preferred method for measuring DNA adducts due to the high selectivity obtained in comparison to, e.g., 32 P-post-labeling technique [27][28][29] . Moreover, recent advances in MS instrumentation providing HRAM data have resulted in gaining more information on the chemical structure of the adduct based on its fragmentation pattern and more accurate elemental composition determination 12,30 . We employed HRMS in DIA mode that permitted stepwise acquisition for the detection of adducts and is useful for its archival nature as samples that have been analyzed earlier can be re-examined for new adducts.…”

Section: Discussionmentioning

confidence: 99%

DNA epigenetic marks are linked to reproductive aberrations in amphipods

Gorokhova

Martella

et al. 2019

Preprint

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Linking exposure to environmental contaminants with diseases is crucial for proposing preventive and regulatory actions. Upon exposure to anthropogenic chemicals, covalent modifications on the genome can drive developmental and reproductive disorders in wild populations, with subsequent effects on the population persistence. Hence, screening of chemical modifications on DNA can be used to provide information on the probability of such disorders in populations of concern. Using a high-resolution mass spectrometry methodology, we identified DNA nucleoside adducts in gravid females of the Baltic amphipods Monoporeia affinis, and linked the adduct profiles to the frequency of embryo malformations in the broods. Twenty-three putative nucleoside adducts were detected in the females and their embryos, and eight modifications were structurally identified using highresolution accurate mass data. To identify which adducts were significantly associated with embryo malformations, partial least squares regression (PLSR) modelling was applied. The PLSR model yielded three adducts as the key predictors: methylation at two different positions of the DNA (5methyl-2'-deoxycytidine and N 6 -methyl-2'-deoxyadenosine) representing epigenetic marks, and a structurally unidentified nucleoside adduct. These adducts predicted the elevated frequency of the malformations with a high classification accuracy (84%). To the best of our knowledge, this is the first application of DNA adductomics for identification of contaminant-induced malformations in field-collected animals. The method can be adapted for a broad range of species and evolve as a new omics tool in environmental health assessment.

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Section: Discussionmentioning

confidence: 99%

DNA epigenetic marks are linked to reproductive aberrations in amphipods

Gorokhova

Martella

et al. 2019

Preprint

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“…In the era of the “exposome,” the integration of various “omics” data is necessary to understand the complex sources of chemical exposures in human diseases . The simultaneous measurement of multiple DNA adducts, or DNA adductomics, by different MS scanning approaches, has recently been reviewed . Due to the complexity of the DNA digest matrix, the ability to discriminate analyte precursors [M + H] + from isobaric interferences at the MS level even with a 5 ppm mass tolerance is insufficient to measure the totality of the DNA adductome, let alone conclusively identify an individual adducts.…”

Section: Methods To Biomonitor Dna Adducts In Humansmentioning

confidence: 99%

DNA adducts: Formation, biological effects, and new biospecimens for mass spectrometric measurements in humans

Yun

Guo

Bellamri

et al. 2018

Mass Spectrometry Reviews

106

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Hazardous chemicals in the environment and diet or their electrophilic metabolites can form adducts with genomic DNA, which can lead to mutations and the initiation of cancer. In addition, reactive intermediates can be generated in the body through oxidative stress and damage the genome. The identification and measurement of DNA adducts are required for understanding exposure and the causal role of a genotoxic chemical in cancer risk. Over the past three decades, P-postlabeling, immunoassays, gas chromatography/mass spectrometry, and liquid chromatography/mass spectrometry (LC/MS) methods have been established to assess exposures to chemicals through measurements of DNA adducts. It is now possible to measure some DNA adducts in human biopsy samples, by LC/MS, with as little as several milligrams of tissue. In this review article, we highlight the formation and biological effects of DNA adducts, and highlight our advances in human biomonitoring by mass spectrometric analysis of formalin-fixed paraffin-embedded tissues, untapped biospecimens for carcinogen DNA adduct biomarker research.

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“…The detection of DNA adducts at levels as low as one per 10 11 nucleotides have been reported using a hybrid Orbitrap MS [ 54 ]. Both targeted and non-targeted MS scan approaches have been employed to identify many DNA chemical modifications [ 35 , 36 , 37 , 55 , 56 , 57 , 58 ].…”

Section: Metabolism Bioactivation and Dna Adducts As Biomarkers mentioning

confidence: 99%

“…Figure 2 shows the fragmentation pathways of modified nucleosides, where the major ions are the chemically modified bases after neutral loss of dR, or in less frequent cases the bases are eliminated as the neutral fragment and the carcinogen moieties retain the charge. These types of MS transitions are usually monitored in the targeted and un-targeted approaches by LC-MS [ 58 , 63 ].…”

Section: Metabolism Bioactivation and Dna Adducts As Biomarkers mentioning

confidence: 99%

“…While most analyses have focused on one to several adducts, different types of MS scanning approaches are being developed to simultaneous scan for multiple types of DNA adducts in the field of DNA adductomics [ 63 ]. Triple quadrupole, quadrupole time-of-flight, ion trap or Orbitrap mass spectrometry instrumentation are being employed in DNA adductomics [ 55 , 58 , 62 , 63 , 110 ]. Our laboratory is developing unbiased non-targeted ion trap and Orbitrap scanning methods to screen for an array of DNA adducts in the human genome in a single assay [ 55 , 58 ].…”

Section: Measurement Of Dna Adducts In Ffpe Tissues By Ihc mentioning

confidence: 99%

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Formalin-Fixed Paraffin-Embedded Tissues—An Untapped Biospecimen for Biomonitoring DNA Adducts by Mass Spectrometry

Yun

Guo

Turesky

2018

Toxics

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The measurement of DNA adducts provides important information about human exposure to genotoxic chemicals and can be employed to elucidate mechanisms of DNA damage and repair. DNA adducts can serve as biomarkers for interspecies comparisons of the biologically effective dose of procarcinogens and permit extrapolation of genotoxicity data from animal studies for human risk assessment. One major challenge in DNA adduct biomarker research is the paucity of fresh frozen biopsy samples available for study. However, archived formalin-fixed paraffin-embedded (FFPE) tissues with clinical diagnosis of disease are often available. We have established robust methods to recover DNA free of crosslinks from FFPE tissues under mild conditions which permit quantitative measurements of DNA adducts by liquid chromatography-mass spectrometry. The technology is versatile and can be employed to screen for DNA adducts formed with a wide range of environmental and dietary carcinogens, some of which were retrieved from section-cuts of FFPE blocks stored at ambient temperature for up to nine years. The ability to retrospectively analyze FFPE tissues for DNA adducts for which there is clinical diagnosis of disease opens a previously untapped source of biospecimens for molecular epidemiology studies that seek to assess the causal role of environmental chemicals in cancer etiology.

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The Future of DNA Adductomic Analysis

Cited by 55 publications

References 68 publications

DNA epigenetic marks are linked to reproductive aberrations in amphipods

DNA epigenetic marks are linked to reproductive aberrations in amphipods

DNA adducts: Formation, biological effects, and new biospecimens for mass spectrometric measurements in humans

Formalin-Fixed Paraffin-Embedded Tissues—An Untapped Biospecimen for Biomonitoring DNA Adducts by Mass Spectrometry

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