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DNA epigenetic marks are linked to embryo aberrations in amphipods
Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
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Number of Authors: 62020 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, article id 655Article in journal (Refereed) Published
Abstract [en]

Linking exposure to environmental stress factors 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 high-resolution 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 (5-methyl-2′-deoxycytidine and N6-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.

Place, publisher, year, edition, pages
2020. Vol. 10, article id 655
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:su:diva-184911DOI: 10.1038/s41598-020-57465-1ISI: 000546559700001PubMedID: 31959811OAI: oai:DiVA.org:su-184911DiVA, id: diva2:1469791
Available from: 2020-09-22 Created: 2020-09-22 Last updated: 2023-04-21Bibliographically 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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Gorokhova, ElenaMartella, GiuliaMotwani, Nisha H.Sundelin, BritaMotwani, Hitesh V.

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