DNA Adducts for Characterization of Exposure

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

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 14349

Special Issue Editor


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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

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Keywords

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

Published Papers (5 papers)

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Research

12 pages, 1167 KiB  
Communication
Current and Future Methodology for Quantitation and Site-Specific Mapping the Location of DNA Adducts
by Gunnar Boysen and Intawat Nookaew
Toxics 2022, 10(2), 45; https://doi.org/10.3390/toxics10020045 - 19 Jan 2022
Cited by 5 | Viewed by 3513
Abstract
Formation of DNA adducts is a key event for a genotoxic mode of action, and their presence is often used as a surrogate for mutation and increased cancer risk. Interest in DNA adducts are twofold: first, to demonstrate exposure, and second, to link [...] Read more.
Formation of DNA adducts is a key event for a genotoxic mode of action, and their presence is often used as a surrogate for mutation and increased cancer risk. Interest in DNA adducts are twofold: first, to demonstrate exposure, and second, to link DNA adduct location to subsequent mutations or altered gene regulation. Methods have been established to quantitate DNA adducts with high chemical specificity and to visualize the location of DNA adducts, and elegant bio-analytical methods have been devised utilizing enzymes, various chemistries, and molecular biology methods. Traditionally, these highly specific methods cannot be combined, and the results are incomparable. Initially developed for single-molecule DNA sequencing, nanopore-type technologies are expected to enable simultaneous quantitation and location of DNA adducts across the genome. Herein, we briefly summarize the current methodologies for state-of-the-art quantitation of DNA adduct levels and mapping of DNA adducts and describe novel single-molecule DNA sequencing technologies to achieve both measures. Emerging technologies are expected to soon provide a comprehensive picture of the exposome and identify gene regions susceptible to DNA adduct formation. Full article
(This article belongs to the Special Issue DNA Adducts for Characterization of Exposure)
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16 pages, 1351 KiB  
Article
Detection of Benzo[a]pyrene Diol Epoxide Adducts to Histidine and Lysine in Serum Albumin In Vivo by High-Resolution-Tandem Mass Spectrometry
by Javier Zurita, Hitesh V. Motwani, Leopold L. Ilag, Vassilis L. Souliotis, Soterios A. Kyrtopoulos, Ulrika Nilsson and Margareta Törnqvist
Toxics 2022, 10(1), 27; https://doi.org/10.3390/toxics10010027 - 08 Jan 2022
Cited by 2 | Viewed by 1981
Abstract
Electrophilic diol epoxide metabolites are involved in the carcinogenicity of benzo[a]pyrene, one of the widely studied polycyclic aromatic hydrocarbons (PAHs). The exposure of humans to this PAH can be assessed by measuring stable blood protein adducts, such as to histidine and [...] Read more.
Electrophilic diol epoxide metabolites are involved in the carcinogenicity of benzo[a]pyrene, one of the widely studied polycyclic aromatic hydrocarbons (PAHs). The exposure of humans to this PAH 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 are expected in humans generally exposed to benzo[a]pyrene from air pollution and the diet. The analytical methods detecting PAH-biomarkers still suffer from low selectivity and/or detectability to enable generation of data for calculation of in vivo doses of specific stereoisomers, for evaluation of risk factors and assessing risk from exposures to PAH. Here, we suggest an analytical methodology based on high-pressure liquid chromatography (HPLC) coupled to high-resolution tandem mass spectrometry (MS) to lower the detection limits as well as to 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 epoxide isomers. The (+)-anti-benzo[a]pyrene diol epoxide adducts could be chromatographically resolved by using an HPLC column with a pentafluorophenyl stationary phase. Interferences were further diminished by the high mass accuracy and resolving power of Orbitrap MS. The achieved method 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. Corresponding adducts to lysine were also quantified. In human serum albumin, the anti-benzo[a]pyrene diol epoxide adducts to histidine were detected in only two out of twelve samples and at a level of approximately 0.1 fmol/mg. Full article
(This article belongs to the Special Issue DNA Adducts for Characterization of Exposure)
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17 pages, 3484 KiB  
Article
Factors Influencing the Formation of Chemical–Hemoglobin Adducts
by Yuko Shimamura, Akina Okuda, Kenya Ichikawa, Ryo Inagaki, Sohei Ito, Hiroshi Honda and Shuichi Masuda
Toxics 2022, 10(1), 2; https://doi.org/10.3390/toxics10010002 - 21 Dec 2021
Cited by 3 | Viewed by 2508
Abstract
Hemoglobin (Hb) adducts have been used as biomarkers for the internal exposure to chemicals. Simultaneous exposure to chemicals that bond with the N-terminal valine of Hb to form adducts, such as glycidol, acrylamide, and glucose, may affect the formation of the individual Hb [...] Read more.
Hemoglobin (Hb) adducts have been used as biomarkers for the internal exposure to chemicals. Simultaneous exposure to chemicals that bond with the N-terminal valine of Hb to form adducts, such as glycidol, acrylamide, and glucose, may affect the formation of the individual Hb adducts. In this study, various factors influencing the formation of chemical–Hb adducts were analyzed using in vitro and in vivo systems. In the in vitro assays, the formation of glycidol– and acrylamide–Hb adducts was altered in the presence of glucose, serum albumin, and other chemicals. In contrast, in the in vivo experiments, glycidol– and acrylamide–Hb adduct formation was unchanged in mice exposed to glycidol and acrylamide. The interaction between glycidol and acrylamide with residues other than the N-terminal valine of Hb was analyzed using the protein thermal shift assay. Glycidol and acrylamide also interacted with amino acid residues other than the N-terminal valine of Hb. The presence of other blood components, such as amino acids, may affect the formation of chemical–Hb adducts. Further research is expected to elucidate the remaining unknown factors that affect the formation of chemical–Hb adducts. Full article
(This article belongs to the Special Issue DNA Adducts for Characterization of Exposure)
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17 pages, 1795 KiB  
Article
Quantitative NanoLC/NSI+-HRMS Method for 1,3-Butadiene Induced bis-N7-guanine DNA-DNA Cross-Links in Urine
by Luke Erber, Samantha Goodman, Caitlin C. Jokipii Krueger, Ivan Rusyn and Natalia Tretyakova
Toxics 2021, 9(10), 247; https://doi.org/10.3390/toxics9100247 - 02 Oct 2021
Cited by 3 | Viewed by 2524
Abstract
1,3-Butadiene (BD) is a common environmental and industrial chemical widely used in plastic and rubber manufacturing and also present in cigarette smoke and automobile exhaust. BD is classified as a known human carcinogen based on evidence of carcinogenicity in laboratory animals treated with [...] Read more.
1,3-Butadiene (BD) is a common environmental and industrial chemical widely used in plastic and rubber manufacturing and also present in cigarette smoke and automobile exhaust. BD is classified as a known human carcinogen based on evidence of carcinogenicity in laboratory animals treated with BD by inhalation and epidemiological studies revealing an increased risk of leukemia and lymphohematopoietic cancers in workers occupationally exposed to BD. Upon exposure via inhalation, BD is bioactivated to several toxic epoxides including 3,4-epoxy-1-butene (EB), 3,4-epoxy-1,2-butanediol (EBD), and 1,2,3,4-diepoxybutane (DEB); these are conjugated with glutathione and excreted as 2-(N-acetyl-L-cystein-S-yl)-1-hydroxybut-3-ene/1-(N-acetyl-L-cystein-S-yl)-2-hydroxybut-3-ene (MHBMA), 4-(N-acetyl-L-cystein-S-yl)-1,2-dihydroxybutane (DHBMA), and 1,4-bis-(N-acetyl-L-cystein-S-yl)butane-2,3-diol (bis-BDMA). Exposure to DEB generates monoalkylated DNA adducts, DNA-DNA crosslinks, and DNA-protein crosslinks, which can cause base substitutions, genomic rearrangements, and large genomic deletions. In this study, we developed a quantitative nanoLC/NSI+-HRMS methodology for 1,4-bis-(gua-7-yl)-2,3-butanediol (bis-N7G-BD) adducts in urine (LOD: 0.1 fmol/mL urine, LOQ: 1.0 fmol/mL urine). This novel method was used to quantify bis-N7G-BD in urine of mice treated with 590 ± 150 ppm BD for 2 weeks (6 h/day, 5 days/week). Bis-N7G-BD was detected in urine of male and female BD-exposed mice (574.6 ± 206.0 and 571.1 ± 163.4 pg/mg of creatinine, respectively). In addition, major urinary metabolites of BD, bis-BDMA, MHBMA and DHBMA, were measured in the same samples. Urinary bis-N7G-BD adduct levels correlated with DEB-derived metabolite bis-BDMA (r = 0.80, Pearson correlation), but not with the EB-derived DNA adducts (EB-GII) or EB-derived metabolites MHBMA and DHBMA (r = 0.24, r = 0.14, r = 0.18, respectively, Pearson correlations). Urinary bis-N7G-BD could be employed as a novel non-invasive biomarker of exposure to BD and bioactivation to its most mutagenic metabolite, DEB. This method will be useful for future studies of 1,3-butadiene exposure and metabolism. Full article
(This article belongs to the Special Issue DNA Adducts for Characterization of Exposure)
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11 pages, 1631 KiB  
Article
nLossFinder—A Graphical User Interface Program for the Nontargeted Detection of DNA Adducts
by Pedro F. M. Sousa, Giulia Martella, K. Magnus Åberg, Bahare Esfahani and Hitesh V. Motwani
Toxics 2021, 9(4), 78; https://doi.org/10.3390/toxics9040078 - 07 Apr 2021
Cited by 12 | Viewed by 2663
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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