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DNA Adductomics for the Biological Effect Assessment of Contaminant Exposure in Marine Sediments
Stockholm University, Faculty of Science, Department of Environmental Science.ORCID iD: 0009-0000-5611-0370
Stockholm University, Faculty of Science, Department of Environmental Science.ORCID iD: 0000-0002-4192-6956
Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).ORCID iD: 0000-0002-5131-6326
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Number of Authors: 62023 (English)In: Environmental Science and Technology, ISSN 0013-936X, E-ISSN 1520-5851, Vol. 57, no 29, p. 10591-10603Article in journal (Refereed) Published
Abstract [en]

Exposure to chemical pollution can induce genetic andepigeneticalterations, developmental changes, and reproductive disorders, leadingto population declines in polluted environments. These effects aretriggered by chemical modifications of DNA nucleobases (DNA adducts)and epigenetic dysregulation. However, linking DNA adducts to thepollution load in situ remains challenging, and thelack of evidence-based DNA adductome response to pollution hampersthe development and application of DNA adducts as biomarkers for environmentalhealth assessment. Here, we provide the first evidence for pollutioneffects on the DNA modifications in wild populations of Baltic sentinelspecies, the amphipod Monoporeia affinis. A workflow based on high-resolution mass spectrometry to screenand characterize genomic DNA modifications was developed, and itsapplicability was demonstrated by profiling DNA modifications in theamphipods collected in areas with varying pollution loads. Then, thecorrelations between adducts and the contaminants level (polycyclicaromatic hydrocarbons (PAHs), trace metals, and pollution indices)in the sediments at the collection sites were evaluated. A total of119 putative adducts were detected, and some (5-me-dC, N-6-me-dA, 8-oxo-dG, and dI) were structurally characterized. The DNAadductome profiles, including epigenetic modifications, differed betweenthe animals collected in areas with high and low contaminant levels.Furthermore, the correlations between the adducts and PAHs were similaracross the congeners, indicating possible additive effects. Also,high-mass adducts had significantly more positive correlations withPAHs than low-mass adducts. By contrast, correlations between theDNA adducts and trace metals were stronger and more variable thanfor PAHs, indicating metal-specific effects. These associations betweenDNA adducts and environmental contaminants provide a new venue forcharacterizing genome-wide exposure effects in wild populations andapply DNA modifications in the effect-based assessment of chemicalpollution. DNA adductome analysis identifiesexposure to environmentalcontaminants in a sentinel species in the Baltic Sea.

Place, publisher, year, edition, pages
2023. Vol. 57, no 29, p. 10591-10603
Keywords [en]
DNA adducts, high-resolution mass spectrometry, biological effect monitoring, environmental contaminants, biomarkers, amphipods as sentinel species
National Category
Environmental Sciences Analytical Chemistry Biochemistry Molecular Biology
Identifiers
URN: urn:nbn:se:su:diva-221132DOI: 10.1021/acs.est.3c00499ISI: 001016699900001PubMedID: 37341092Scopus ID: 2-s2.0-85164373624OAI: oai:DiVA.org:su-221132DiVA, id: diva2:1798191
Available from: 2023-09-18 Created: 2023-09-18 Last updated: 2025-02-20Bibliographically approved
In thesis
1. DNA adductomics: Method development and integration in biological effect monitoring
Open this publication in new window or tab >>DNA adductomics: Method development and integration in biological effect monitoring
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Environmental omics can provide informative biomarkers for identifying pathologies or physiological responses to environmental change. Nucleic acid adductomics, one of the newest omics techniques, is particularly well suited for assessing exposure and effects of environmental contaminants because the technique can capture modifications at the (epi)genome level. However, identifying potential adduct-biomarkers is challenging, especially in non-model organisms. Therefore, the primary aims of this study were to improve the methodology and explore the applicability of nucleic acid adductomics in environmental monitoring of the biological effects of contaminants, using amphipods as sentinel species.

From a methodology perspective, this thesis presents a gradual progression in screening and detecting DNA modifications. The mass spectrometry (MS) based approach for identifying candidate DNA adducts utilized the characteristic neutral loss of deoxyribose. In Paper I, the data generated from high resolution MS in Full Scan-Data independent Acquisition mode were analyzed manually using the fragmentation pattern of nucleoside adduct ions. In Paper II, processing time and efficiency were significantly improved by the development of nLossFinder software. Further, TraceFinder software was combined and used to evaluate and quantify detected adducts (Paper III). Another important development was a simultaneous approach for analysis of  both DNA and RNA adducts in a single MS run presented in Paper IV

The analysis of amphipod samples based on the existing approaches and methods developed in this thesis showed that reproductive pathologies identified by the microscopic analysis were associated with specific DNA modifications that can be used to classify field-collected individuals according to their health status (Paper I). Moreover, epigenetic marks were the most influential adducts for this classification. Finally, the adduct profile of amphipods differed between the areas with relatively high and low contamination loads based on PAH and trace metal concentrations in the sediment (Paper III). Also, significant correlations were found between DNA adducts and specific contaminants.

These method developments and findings uniquely contribute to the field of environmental omics, providing tools for data processing and demonstrating the applicability of nucleic acid adductomics in environmental health research and biological effect monitoring.

Place, publisher, year, edition, pages
Stockholm: Department of Environmental Science, Stockholm University, 2023. p. 34
Keywords
DNA adducts, Nucleic acids, High-resolution mass spectrometry, Data-independent acquisition, Biological effect monitoring, Environmental contaminants, Biomarkers, Amphipods as sentinel species
National Category
Environmental Sciences Analytical Chemistry
Research subject
Environmental Sciences
Identifiers
urn:nbn:se:su:diva-216618 (URN)978-91-8014-320-2 (ISBN)978-91-8014-321-9 (ISBN)
Public defence
2023-06-09, Högbomsalen, Geovetenskapens Hus, Svante Arrhenius väg 12, Stockholm, Stockholm, 10:00 (English)
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Available from: 2023-05-15 Created: 2023-04-21 Last updated: 2023-10-04Bibliographically approved

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Martella, GiuliaGorokhova, ElenaM. de Sousa, Pedro F.Sundelin, BritaMotwani, Hitesh Vijay

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Martella, GiuliaGorokhova, ElenaM. de Sousa, Pedro F.Sundelin, BritaMotwani, Hitesh Vijay
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