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.
|Original language||English (US)|
|State||Published - Jan 20 2020|
Bibliographical noteFunding Information:
This work was financially supported by the Swedish Research Council Formas (2017-00864), the Swedish Institute (23716/2018), the Erasmus+ program, the Department of Environmental Science and Analytical Chemistry at Stockholm University, and the United States National Institutes of Health (R01CA095039).
© 2020, The Author(s).
- DNA Adducts/genetics
- DNA Methylation
- Embryo, Nonmammalian/abnormalities
- Environmental Exposure/adverse effects
- Epigenesis, Genetic
- Water Pollutants, Chemical/adverse effects
PubMed: MeSH publication types
- Research Support, Non-U.S. Gov't
- Journal Article
- Research Support, N.I.H., Extramural