ArticleGenes and environment : the official journal of the Japanese Environmental Mutagen Society2021
Mass spectrometric profiling of DNA adducts in the human stomach associated with damage from environmental factors.
Article in Genes and environment : the official journal of the Japanese Environmental Mutagen Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 29 citations in OpenAlex.
- Multi-adductomics: Advancing mass spectrometry techniques for comprehensive exposome characterization.Trends in analytical chemistry : TRAC · 2024Article
- DNA Adductomics: A Narrative Review of Its Development, Applications, and Future.Biomolecules · 2024Review
- Nucleic acid adductomics - The next generation of adductomics towards assessing environmental health risks.The Science of the total environment · 2023Article
- Pathways to Identify ElectrophilesChemical research in toxicology · 2022Article
- Current and Future Methodology for Quantitation and Site-Specific Mapping the Location of DNA Adducts.Toxics · 2022Article
- A DNA adductome analysis revealed a reduction in the global level of C5-hydroxymethyl-2'-deoxycytidine in the non-tumoral upper urinary tract mucosa of urothelial carcinoma patients.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2021Article
- Geospatial Assessments of DNA Adducts in the Human Stomach: A Model of Field Cancerization.Cancers · 2021Review
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16 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundA comprehensive understanding of DNA adducts, one of the most plausible origins of cancer mutations, is still elusive, especially in human tissues in clinical settings. Recent technological developments have facilitated the identification of multiple DNA adducts in a single experiment. Only a few attempts toward this "DNA adductome approach" in human tissues have been reported. Geospatial information on DNA adducts in human organs has been scarce.
aimMass spectrometry of human gastric mucosal DNA was performed to identify DNA adducts associated with environmental factors. MATERIALS AND
methodsFrom 59 subjects who had received gastrectomy for gastric cancer, 306 samples of nontumor tissues and 15 samples of tumors (14 cases) were taken for DNA adductome analysis. Gastric nontumor tissue from autopsies of 7 subjects without gastric cancer (urothelial cancer, hepatocellular carcinoma, lung cancer each; the other four cases were without any cancers) was also investigated. Briefly, DNA was extracted from each sample with antioxidants, digested into nucleosides, separated by liquid chromatography, and then electrospray-ionized. Specific DNA adducts were identified by mass/charge number and column retention time compared to standards. Information on lifestyle factors such as tobacco smoking and alcohol drinking was taken from the clinical records of each subject.
resultsSeven DNA adducts, including modified bases, C5-methyl-2'-deoxycytidine, 2'-deoxyinosine, C5-hydroxymethyl-2'-deoxycytidine, N6-methyl-2'-deoxyadenosine, 1,N6-etheno-2'-deoxyadenosine, N6-hydroxymethyl-2'-deoxyadenosine, and C8-oxo-2'-deoxyguanosine, were identified in the human stomach and characterized. Intraindividual differences according to the multiple sites of these adducts were noted but were less substantial than interindividual differences. N6-hydroxymethyl-2'-deoxyadenosine was identified in the human stomach for the first time. The amount of C5-hydroxymethyl-2'-deoxycytidine was higher in the stomachs of subjects without gastric cancer than in the nontumor and tumor portions of the stomach in gastric cancer patients. Higher levels of 1,N6-etheno-2'-deoxyadenosine were detected in the subjects who reported both smoking and drinking than in those without these habits. These DNA adducts showed considerable correlations with each other.
conclusionsWe characterized 7 DNA adducts in the nontumor portion of the human stomach in both gastric cancer subjects and nongastric cancer subjects. A reduction in C5-hydroxymethyl-dC even in the nontumor mucosa of patients with gastric cancer was observed. Smoking and drinking habits significantly influenced the quantity of one of the lipid peroxidation-derived adducts, etheno-dA. A more expansive DNA adductome profile would provide a comprehensive understanding of the origin of human cancer in the future.
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