Traditional analytical methods for DNA adducts. The detection of DNA adducts has commonly been conducted using immunochemical \cite{Müller1982} and ³²P-postlabelling \cite{Poirier2000} assays. Although useful, these assays do not provide chemical or structural information about the adducts to trace back to specific exposures. Moreover, these techniques have significant limitations: the immunochemical method is not sensitive enough to detect DNA adducts at trace levels and requires an antibody to each chemical. Albeit highly sensitive, ³²P-postlabelling involves radioactive phosphorus usage, implying safety concerns and regulatory challenges  \cite{Hwa2020}. The method is also labour-intensive and further complicated by highly variable labelling efficiency \cite{Totsuka_1996}. Nowadays, researchers need to adhere to strict safety protocols for handling radioactive materials and waste disposal, which has led to a gradual disappearance of laboratories willing to conduct these measurements. Moreover, key limitations include the scarcity of information on the detected DNA adduct structure and occasional co-migration of adducts on the thin layer chromatography plate \cite{Phillips_2007}. These challenges collectively impede the chemical structural characterization and identification of the adducts.  

A novel approach to measure old biomarker. Nowadays, one of the most powerful techniques for detecting and quantifying DNA adducts is liquid chromatography-mass spectrometry (LC-MS). Using high-resolution mass spectrometry (HRMS), sensitive and selective analytical methods for detecting and identifying DNA adducts in the genome have been developed \cite{Hemeryck_2016} and successfully applied in human health research \cite{Hwa2020,Totsuka2021} and ecotoxicological \cite{Gorokhova2020,Martella2023} diagnostics of adverse effects due to chemical exposure. Instead of analyzing a few adducts from a specific chemical exposure ( (i.e., bottom-up approach), HRMS gives the possibility to screen for DNA adducts from multiple classes of exposure, an “adductomics” approach. Thus, this is a new OMICS approach, with both target and non-targeted analytical methods available to comprehensively investigate the adductome via screening for all known and unknown adducts in the genome (i.e., top-down approach). Various modification types, e.g., bulky PAH-adducts, methylation and oxidation, can be analyzed in a single sample by HRMS, including the determination of their chemical structures, which is useful for exposure diagnostics \cite{Balbo2014,Villalta2017}. Thus, the current capacity for DNA adduct characterization is superior to the classical assays, advocating this OMICS approach to detect and monitor the biological effects of contaminants \cite{Martella2023}.

Using various cell types and matrices, several DNA adductomics methods based on LS-HRMS have been developed for applications in human toxicology \cite{Balbo2014a,Guo2018,Hemeryck2017}. These developments are poised to be applicable to any biological sample and allow proposing a workflow for low- and high-mass DNA adduct analysis in wildlife as a part of ecotoxicological surveillance \cite{Martella2023}.  

Test organisms. Any plant or animal tissue is suitable for the analysis, including the whole body (for small-sized planktonic and benthic animals as well as embryos), blood, liver and muscle tissues. If fertilized eggs or embryos are present in small specimens, they should be dissected out and either analyzed separately or not included in the female DNA samples to avoid the natural ontogenetic variability in the epigenetic DNA modifications related to embryogenesis \cite{Gorokhova2020}.  In fish, liver and muscle tissues are commonly used as test tissues, and more work is needed to identify target tissues and organs for specific adducts if we are to improve the diagnostic properties of the method.