DNA Adduct Analysis and Carcinogenic Mechanisms

DNA adduct analysis probes the covalent attachment of electrophilic agents—whether environmental pollutants, dietary carcinogens or endogenous by-products of metabolism—to nucleobases. Such adducts represent the molecular lesions that can obstruct normal replication and initiate mutagenic events. High-resolution liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) has enabled untargeted “adductomics” to chart the full complement of DNA lesions across tissues, species and exposure scenarios. The resulting data have elucidated age-, sex- and organ-specific patterns of damage, informed mechanistic models of initiation and progression in chemical carcinogenesis, and revealed critical thresholds for repair-mediated genome maintenance. Integration of adduct quantitation with biochemical assays of nucleotide excision repair, base excision repair and mismatch repair pathways has refined risk assessment paradigms for genotoxic agents. In parallel, the emergence of adduct profiling as a biomarker platform supports biomonitoring of human exposures, ecological assessments of pollution and the development of targeted strategies for chemoprevention.

Research from Nature Portfolio

Recent studies have demonstrated the power of adductomic analysis in environmental health. In a field-based investigation of benthic amphipods, high-resolution mass spectrometry identified twenty-three putative nucleoside adducts, of which eight were structurally characterised. Multivariate modelling pinpointed two epigenetic methylation marks—5-methyl-2′-deoxycytidine and N6-methyl-2′-deoxyadenosine—and an additional unknown adduct as strong predictors of embryonic malformations, achieving classification accuracy in excess of 80 percent. This work illustrates how comprehensive profiling of DNA modifications can serve as an omics tool to link contaminant exposure with developmental outcomes in wildlife populations.

DNA Adduct Analysis and Carcinogenic Mechanisms publication trend

The graph below shows the total number of articles in dna adduct analysis and carcinogenic mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

DNA adduct: A covalent modification of a nucleobase by a reactive chemical species.

Adductomics: Comprehensive, high-resolution profiling of DNA adducts using advanced mass spectrometry.

High-resolution mass spectrometry: An analytical technique that provides accurate mass measurements and fine structural information.

Epigenetic mark: A chemical modification on DNA that influences gene expression without altering the genetic sequence.

Carcinogenesis: The multistage process by which normal cells transform into cancerous cells through genetic and epigenetic alterations.

References

1. DNA epigenetic marks are linked to embryo aberrations in amphipods. Scientific Reports (2020).
2. Discovery adductomics provides a comprehensive portrait of tissue-, age- and sex-specific DNA modifications in rodents and humans. Nucleic Acids Research (2023).
3. Exploration and optimization of extraction, analysis and data normalization strategies for mass spectrometry-based DNA adductome mapping and modeling. Analytica Chimica Acta (2023).
4. DNA Adductomics for the Biological Effect Assessment of Contaminant Exposure in Marine Sediments. Environmental Science and Technology (2023).
5. Mode of action-based risk assessment of genotoxic carcinogens. Archives of Toxicology (2020).