Special Issue "DNA Adducts for Characterization of Exposure"

A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Exposome".

Deadline for manuscript submissions: 15 November 2021.

Special Issue Editor

Dr. Hitesh V. Motwani
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Guest Editor
Department of Environmental Science, Stockholm University, Stockholm, SE, 10691, Sweden
Interests: genotoxicity; epigenetics; exposomics; contaminants; risk assessment

Special Issue Information

Dear colleagues,

The field of DNA adductomics  has been evolving as a new omics approach in toxicology research. This has mainly been possible due to advances in analytical techniques, in particular, high-resolution mass spectrometry (HRMS). Characterizing the structural modifications to DNA, as part of adductomics, can allow to identify certain exposures related to environmental stress, both genotoxic and nongenotoxic. The exposure could be related to potential carcinogens, for example if the detected adducts are formed from covalent binding to electrophilic reactive compounds/metabolites. Alternatively, oxidative adducts arising from reactive oxygen species, if not repaired, might lead to mutations. Improving chromatographic separation, data processing and structural elucidation, as well as developing approaches for the use of adduct measurements in risk  assessment procedures are some of the challenges in the field.

In this issue, we invite high-quality original research papers, short communications, and reviews related to linkages between DNA adducts and exposure assessment. In addition to exposure to humans, environmental stress factors and exposure to wild-life species are areas of concern. Topics of interest include (but are not limited to) reactive metabolites, oxidative stress, methylation as epigenetic marker and MS-based development and applications of adductomics. Related articles on protein adducts and RNA adducts may also be considered.

Dr. Hitesh V. Motwani
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • biomarkers
  • adducts
  • mass spectrometry
  • reactive metabolites
  • DNA methylation
  • environmental stress
  • toxicology

Published Papers (1 paper)

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Research

Article
nLossFinder—A Graphical User Interface Program for the Nontargeted Detection of DNA Adducts
Toxics 2021, 9(4), 78; https://doi.org/10.3390/toxics9040078 - 07 Apr 2021
Viewed by 736
Abstract
DNA adductomics is a relatively new omics approach aiming to measure known and unknown DNA modifications, called DNA adducts. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) has become the most common method for analyzing DNA adducts. Recent advances in the field of mass spectrometry have [...] Read more.
DNA adductomics is a relatively new omics approach aiming to measure known and unknown DNA modifications, called DNA adducts. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) has become the most common method for analyzing DNA adducts. Recent advances in the field of mass spectrometry have allowed the possibility to perform a comprehensive analysis of adducts, for instance, by using a nontargeted data-independent acquisition method, with multiple precursor m/z windows as an inclusion list. However, the generated data are large and complex, and there is a need to develop algorithms to simplify and automate the time-consuming manual analysis that has hitherto been used. Here, a graphical user interface (GUI) program was developed, with the purpose of tracking a characteristic neutral loss reaction from tandem mass spectrometry of the nucleoside adducts. This program, called nLossFinder, was developed in the MATLAB platform, available as open-source code. Calf thymus DNA was used as a model for method optimization, and the overall adductomics approach was applied to DNA from amphipods (Monoporeia affinis) collected within the Swedish National Marine Monitoring Program. In the amphipod DNA, over 150 putative adducts were found in comparison to 18 using a manual approach in a previous study. The developed program can improve the processing time for large MS data, as it processes each sample in a few seconds, and hence can be applicable for high-throughput screening of adducts. Full article
(This article belongs to the Special Issue DNA Adducts for Characterization of Exposure)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: nLossFinder – A graphical user interface program for non-targeted detection of DNA adducts
Authors: Pedro F.M. Sousa; Giulia Martella; K. Magnus Åberg; Bahare Esfahani; Hitesh V. Motwani
Affiliation: Stockholm University
Abstract: DNA adductomics is a relatively new omics approach aiming to measure the known and unknown modifications on the nucleosides. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has become the most common method for analyzing DNA adducts. The recent advances in the field of mass spectrometry has allowed the possibility to perform a comprehensive analysis of adducts, for instance, by using a non-targeted data independent acquisition method, with multiple precursor m/z windows as an inclusion list. However, the generated data is large and complex and there has been a need to develop algorithms to simplify and automate the time-consuming manual analysis that hitherto has been used. Here, a graphical user interface (GUI) program has been developed, with the purpose of tracking a characteristic neutral loss reaction from tandem mass spectrometry of the nucleoside adducts. This program, called nLossFinder, has been developed in MATLAB platform and the code is available as open source. Calf thymus DNA was used as a model for method optimization, and the overall adductomics approach was applied to DNA from amphipods (Monoporeia affinis) collected within the Swedish National Marine Monitoring Program. In the amphipod DNA over 150 putative adducts were found in comparison to 18 using manual approach in a previous work. The developed program can improve the processing time for large MS-data, as it processes each sample in few seconds, and hence can be applicable for high-throughput screening of adducts.

Title: Detection of benzo[a]pyrene diol epoxide adducts to histidine and lysine in serum albumin in vivo by high-resolution-tandem mass spectrometry
Authors: Javier Zurita; Hitesh V. Motwani; Leopold L. Ilag; Vassilis L. Souliotos; Soterios A. Kyrtopoulos; Ulrika Nilsson; Margareta Törnqvist
Affiliation: 1 Department of Environmental Science and Analytical Chemistry, Stockholm University, SE-106 91 Stockholm, Sweden 2 Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, Athens, Greece
Abstract: Electrophilic diol epoxide metabolites are involved in the carcinogenicity of benzo[a]pyrene, one of the widely studied polycyclic aromatic hydrocarbons. The exposure of humans to this compound can be assessed by measuring stable blood protein adducts, such as to histidine and lysine in serum albumin, from their reactive metabolites. In this respect, measurement of the adducts originating from the genotoxic (+)-anti-benzo[a]pyrene diol epoxide is of interest. However, these are difficult to measure at such low levels as is expected in humans with general exposure to benzo[a]pyrene from air pollution and the diet. The analytical methods detecting PAH-biomarkers today still suffer from low selectivity and/or detectability to enable generation of data for calculation of in vivo doses of specific stereoisomers and for statistical evaluation in assessing risk factors. Here, we suggest an analytical methodology based on high pressure liquid chromatography coupled to high-resolution tandem mass spectrometry to lower the detection limits as well as increase the selectivity with improvements in both chromatographic separation and mass determination. Method development was performed using serum albumin alkylated in vitro by benzo[a]pyrene diol epoxides. The (+)-anti-benzo[a]pyrene diol epoxide adducts could be chromatographically resolved by using a pentafluorophenyl HPLC column and interferences were further diminished by the high mass accuracy and resolving power of the Orbitrap. The achieved detection limit for the (+)-anti-benzo[a]pyrene diol epoxide adduct to histidine was approximately 4 amol/mg serum albumin. This adduct as well as the adducts to histidine from (-)-anti- and (+/-)-syn-benzo[a]pyrene diol epoxide were quantified in the samples from benzo[a]pyrene exposed mice. The (+)-anti-benzo[a]pyrene diol epoxide adduct to histidine could also be detected at approximately 8 amol/mg in one of the human in vivo samples.

Title: Isotope dilution NanoLC/ESI+ -HRMS quantitation of urinary bis-N7-guanine DNA-DNA crosslink adducts in urine
Authors: Natalia Tretyakova
Affiliation: University of Minnesota Twin Cities, Department of Medicinal Chemistry, Minneapolis, United States

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