Pivotal Role of Mass Spectrometry for the Assessment of Exposure to Reactive Chemical Contaminants: From the Exposome to the Adductome DOI
Laurent Debrauwer, Loïc Mervant, Olivier Laprévôte

et al.

Mass Spectrometry Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 2, 2024

ABSTRACT A large part of the Human chemical exposome is now well characterized, and its health effects has been widely documented, although precise causal links remain difficult to establish. In parallel, genetic factors only were shown contribute less than 30% various pathologies. Therefore, environmental may represent predominant cause chronic diseases. Mass Spectrometry established for many years as a main “gold standard” in this field due performances both sensitivity selectivity. However, some unstable or highly reactive compounds escape their detection biological samples because short half‐life stable metabolites, if any, can be used exposure assessment. These electrophilic molecules are known bind covalently nucleophilic body form what commonly called adducts. The study adducts formed with DNA, proteins glutathione, nowadays adductomics, provide additional toxicologically relevant information biomonitoring studies. This review describes particular related mass spectrometric methods developed therein. Three dedicated parts devoted contribution spectrometry respectively assessment DNA modifications, protein reaction glutathione.

Language: Английский

Screening DNA Damage in the Rat Kidney and Liver by Untargeted DNA Adductomics DOI

Nagarjunachary Ragi,

Scott J. Walmsley,

Foster C. Jacobs

et al.

Chemical Research in Toxicology, Journal Year: 2024, Volume and Issue: 37(2), P. 340 - 360

Published: Jan. 9, 2024

Air pollution, tobacco smoke, and red meat are associated with renal cell cancer (RCC) risk in the United States Western Europe; however, chemicals that form DNA adducts initiate RCC mainly unknown. Aristolochia herbaceous plants used for medicinal purposes Asia worldwide. They a significant factor upper tract urothelial carcinoma (UTUC) to lesser extent. The aristolochic acid (AA) 8-methoxy-6-nitrophenanthro-[3,4-d]-1,3-dioxolo-5-carboxylic (AA-I), component of herbs, contributes UTUC Asian cohorts Croatia, where AA-I exposure occurs from ingesting contaminated wheat flour. adduct AA-I, 7-(2′-deoxyadenosin-N6-yl)-aristolactam I, is often detected patients UTUC, its characteristic A:T-to-T:A mutational signature oncogenes tumor suppressor genes AA-associated UTUC. Identifying parenchyma pelvis caused by other crucial gaining insights into unknown etiologies. We employed untargeted screening wide-selected ion monitoring tandem mass spectrometry (wide-SIM/MS2) nanoflow liquid chromatography/Orbitrap detect formed rat kidneys liver mixture 13 environmental, tobacco, dietary carcinogens may contribute RCC. Twenty were detected. 3-nitrobenzanthrone (3-NBA), an atmospheric pollutant, most abundant. nitrophenanthrene moieties 3-NBA undergo reduction their N-hydroxy intermediates 2′-deoxyguanosine (dG) 2′-deoxyadenosine (dA) adducts. also discovered 2′-deoxycytidine dA dG 10-methoxy-6-nitro-phenanthro-[3,4-d]-1,3-dioxolo-5-carboxylic (AA-III), isomer minor herbal extract assayed, signifying AA-III potent kidney DNA-damaging agent. roles AA-III, nitrophenanthrenes, nitroarenes damage human warrant further study. Wide-SIM/MS2 powerful scanning technology discovery etiology characterization.

Language: Английский

Citations

6
DNA Modifications: Biomarkers for the Exposome? DOI

Carolina Möller,

Jazmine Virzi,

Yuan-Jhe Chang

et al.

Environmental Toxicology and Pharmacology, Journal Year: 2024, Volume and Issue: 108, P. 104449 - 104449

Published: April 16, 2024

Language: Английский

Citations

4
Investigating the origins of the mutational signatures in cancer DOI Creative Commons
Gunnar Boysen, Ludmil B. Alexandrov, Raheleh Rahbari

et al.

Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(1)

Published: Jan. 7, 2025

Abstract Most of the risk factors associated with chronic and complex diseases, such as cancer, stem from exogenous endogenous exposures experienced throughout an individual’s life, collectively known exposome. These can modify DNA, which subsequently lead to somatic mutations found in all normal tumor tissues. Understanding precise origins specific has been challenging due multitude DNA adducts (i.e. adductome) their diverse positions within genome. Thus far, this limitation prevented researchers precisely linking subsequent mutational outcomes. Indeed, many common observed human cancers appear originate error-prone processes. Consequently, it remains unclear whether these result exposure-induced adducts, or arise indirectly processes are a combination both. In review, we summarize approaches that aim bridge our understanding mechanism by exposure leads damage then mutation highlight some remaining challenges shortcomings fully supporting paradigm. We emphasize need integrate cellular adductomics, long read-based mapping, single-molecule duplex sequencing native molecules advanced computational analysis. This proposed holistic approach aims unveil causal connections between key modifications landscape, they external exposures, internal both, thereby addressing questions cancer biology.

Language: Английский

Citations

0
Advances in the mechanistic understanding, biological consequences, and measurement of DNA adducts induced by tobacco smoke and e-cigarette aerosol: A review DOI

Xinyun Zhang,

Jiapeng Leng,

Ling Lv

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 306, P. 141574 - 141574

Published: Feb. 27, 2025

Language: Английский

Citations

0
Development of an untargeted DNA adductomics method by ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry DOI Creative Commons
Giorgia La Barbera,

Marshal Spenser Shuler,

Søren Hammershøj Beck

et al.

Talanta, Journal Year: 2024, Volume and Issue: 282, P. 126985 - 126985

Published: Oct. 5, 2024

Language: Английский

Citations

2
DNA Adductomics: A Narrative Review of Its Development, Applications, and Future DOI Creative Commons
Mengqiu Cao, Xinyu Zhang

Biomolecules, Journal Year: 2024, Volume and Issue: 14(9), P. 1173 - 1173

Published: Sept. 19, 2024

DNA adductomics is the global study of all adducts and was first proposed in 2006 by Matsuda group. Its development has been greatly credited to advances mass spectrometric techniques, particularly tandem multiple-stage spectrometry. In fact, liquid chromatography-mass spectrometry (LC-MS)-based methods are virtually sole technique with practicality for adductomic studies date. At present, primarily used as a tool search adducts, known unknown, providing evidence exposure exogenous genotoxins and/or molecular mechanisms their genotoxicity. Some discovered this way have potential predict cancer risks be associated adverse health outcomes. successfully identify determine carcinogens that may contribute etiology certain cancers, including bacterial an N-nitrosamine. Also using approach, multiple observed show age dependence serve aging biomarkers. These achievements highlight capability power medicine, biological science, environmental science. Nonetheless, still its infancy, great expected future.

Language: Английский

Citations

1
Development of an untargeted DNA adductomics method by ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry DOI Creative Commons
Giorgia La Barbera,

Marshal Spenser Shuler,

Søren Hammershøj Beck

et al.

Published: April 29, 2024

Background: Genotoxicants originating from inflammation, diet, and environment can covalently modify DNA, possibly initiating the process of carcinogenesis. DNA adducts have been known for long, but old methods allowed to target only a few at time, not providing global picture “DNA adductome”. adductomics is new research field, aiming screen unknown by high resolution mass spectrometry (HRMS). However, presents several analytical challenges such as need sensitivity development effective screening approaches identify novel adducts. Results: In this work, sensitive untargeted method was developed using ultra-high performance liquid chromatography (UHPLC) coupled via an ESI source quadrupole-time flight spectrometric instrumentation. Mobile phases with ammonium bicarbonate gave best signal enhancement. The MS capillary voltage, cone detector voltage had most effect on response A low adsorption vial selected reducing analyte loss. Hybrid surface-coated columns were tested optimized applied analyse in calf thymus, cat colon, human colon performing MSE acquisition (all-ion fragmentation acquisition) loss deoxyribose nucleobase fragment ions. Fifty-four tentatively identified, hereof 38 never reported before. Significance: This first study tissue, one studies literature reporting identification number unknowns. demonstrates promising results application future investigating potential cancer-causing factors.

Language: Английский

Citations

1
Multi-adductomics: Advancing mass spectrometry techniques for comprehensive exposome characterization DOI
Mu‐Rong Chao, Yuan-Jhe Chang, Marcus S. Cooke

et al.

TrAC Trends in Analytical Chemistry, Journal Year: 2024, Volume and Issue: 180, P. 117900 - 117900

Published: Aug. 5, 2024

Language: Английский

Citations

0
Pivotal Role of Mass Spectrometry for the Assessment of Exposure to Reactive Chemical Contaminants: From the Exposome to the Adductome DOI
Laurent Debrauwer, Loïc Mervant, Olivier Laprévôte

et al.

Mass Spectrometry Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 2, 2024

ABSTRACT A large part of the Human chemical exposome is now well characterized, and its health effects has been widely documented, although precise causal links remain difficult to establish. In parallel, genetic factors only were shown contribute less than 30% various pathologies. Therefore, environmental may represent predominant cause chronic diseases. Mass Spectrometry established for many years as a main “gold standard” in this field due performances both sensitivity selectivity. However, some unstable or highly reactive compounds escape their detection biological samples because short half‐life stable metabolites, if any, can be used exposure assessment. These electrophilic molecules are known bind covalently nucleophilic body form what commonly called adducts. The study adducts formed with DNA, proteins glutathione, nowadays adductomics, provide additional toxicologically relevant information biomonitoring studies. This review describes particular related mass spectrometric methods developed therein. Three dedicated parts devoted contribution spectrometry respectively assessment DNA modifications, protein reaction glutathione.

Language: Английский

Citations

0