Looking ahead
DNA adductomics is a new research area that offers structural insights into chemical modifications of the nucleic acids and a platform for the discovery of exposure and effect biomarkers. One of the main challenges for introducing DNA adductome analysis in environmental monitoring is the complexity and variability of environmental exposures. Moving forward, we need to prioritize the structural identification of these modifications, establishing connections between candidate DNA adducts and potential causative chemicals or metabolites. Moreover, identifying potential exposures to elucidate responses across various species is crucial. Simultaneously, experimental studies are essential to validate the relationships between specific adducts, exposure agents, and health outcomes, which requires controlled exposure systems to establish critical levels of adduct biomarkers based on toxicity data.
In a recent development, we introduced a novel approach for concurrent RNA and DNA adductomics utilizing a single injection on LC-Orbitrap HRMS instrumentation \cite{Martella2023a}, with the simultaneous detection of RNA adducts, measured through modified ribonucleosides, and DNA adducts, measured through modified 2′-deoxyribonucleosides. RNA molecules play multiple roles in cellular function, serving not only as genetic materials but also providing structural support and catalyzing essential functions within cells. Similar to DNA and due to the nucleophilicity of their nucleobases, RNA molecules are susceptible to reacting with electrophilic species, leading to adduct formation. In cases of toxic adduction, the adducted RNA has been associated with a variety of diseases in humans \cite{Zhou2022}. However, despite being evident and detectable, the physiological and pathological functions of RNA adduction remain poorly understood and virtually nothing is known about pathological responses in non-mammalian species. To validate the efficacy of this multi-adductomics workflow, we conducted a proof-of-principle study \cite{Martella2023a}, demonstrating its application in the analysis of amphipod RNA and DNA adducts. The discovery of new RNA modifications opens new venues in understanding their biological significance for transcriptome and the impact of contaminants on the adductome, which can support future applications of specific adducts as molecular biomarkers in environmental monitoring. Thus, analyzing both DNA and RNA in adductome studies would provide a more comprehensive understanding of the molecular impacts of exposure to various agents and on different time scales.
Regional monitoring programmes should consider the diverse analytical goals (targeted or untargeted), varying DNA amounts in the sentinel species, distinct DNA adduct levels, and considerations like the nature of adducts (hydrophobic vs hydrophilic) and instrument availability when designing the sampling scheme. Consequently, thoughtful consideration of these factors is essential to determine the most suitable approach for a given context. Continued improvements in mass spectrometry and other analytical techniques will enhance the sensitivity, selectivity, and speed of DNA adduct detection. To this end, centralized facilities allow for efficient use of resources, both in terms of equipment and personnel. This can lead to cost-effectiveness and a more streamlined approach to handling the complexities associated with DNA adduct analysis. Moreover, designated facilities are more likely to adhere to recognized standards and guidelines in DNA adduct analysis, and compliance with established protocols enhances the credibility and acceptance of the generated data in scientific and regulatory contexts. Finally, centralized facilities often encourage collaboration among researchers, laboratories, and institutions. This collaborative environment facilitates the exchange of knowledge, expertise, and best practices, driving forward the field of environmental DNA adductomics.