Urinary DNA adductomics – A novel approach for exposomics

Cooke, Marcus S.; Hu, Chiung‐Wen; Chang, Yuan-Jhe; Chao, Mu‐Rong

doi:10.1016/j.envint.2018.10.041

Cited by 34 publications

(23 citation statements)

References 58 publications

(73 reference statements)

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“…23 Using urine samples, Chang et al 24 detected significantly increased levels of DNA adducts in N-nitrosamine-treated mice than in control mice. Additionally, Cooke et al 25 presented human urinary adductome maps, which detected both 2′-deoxyribonucleoside and nucleobase adducts, but nucleobase adducts were found to be the major adducts. Although these studies indicate the utility of the urinary adductome approach, further studies are warranted to validate the technique.…”

Section: Limitations Of Dna Adductome Analysis and Solutionsmentioning

confidence: 99%

New horizons of DNA adductome for exploring environmental causes of cancer

Totsuka¹,

Watanabe

Lin

2020

Cancer Science

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Environmental factors contribute substantially to cancer development. 1 Exposure to mutagenic or carcinogenic compounds in the environment occurs from multiple sources, including environmental pollution, occupation, lifestyle choices, and pharmaceutical use. Once absorbed in the body, chemical substances interact with DNA bases, leading to the formation of DNA adducts. Most of the DNA adducts are repaired by cellular processes, but the remaining, unrepaired adducts can cause genomic mutations during DNA replication, which results in genomic instability and could promote carcinogenesis. 1,2 DNA adducts play a critical role in early stages of carcinogenesis by initiating mutagenesis, 2 and serving as markers of exposure to environmental carcinogens. 3 Moreover, they indicate the etiology of human cancer, as exemplified by AFB1. 4-6 Detection of the AFB1-DNA adduct, coupled with identification of distinct mutation patterns in TP53 induced by this adduct, has provided convincing

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Section: Limitations Of Dna Adductome Analysis and Solutionsmentioning

confidence: 99%

New horizons of DNA adductome for exploring environmental causes of cancer

Totsuka¹,

Watanabe

Lin

2020

Cancer Science

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“…Our initial method comprised the analysis of urinary damaged 2′-dN only. Noting that we were missing damaged nucleobases (the products of BER) from our analyses, we extended the method for their inclusion [ 301 ].…”

Section: The Futurementioning

confidence: 99%

Biomarkers of nucleic acid oxidation – A summary state-of-the-art

Chao

Evans

et al. 2021

Redox Biology

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Oxidatively generated damage to DNA has been implicated in the pathogenesis of a wide variety of diseases. Increasingly, interest is also focusing upon the effects of damage to the other nucleic acids, RNA and the (2′-deoxy-)ribonucleotide pools, and evidence is growing that these too may have an important role in disease. LC-MS/MS has the ability to provide absolute quantification of specific biomarkers, such as 8-oxo-7,8-dihydro-2′-deoxyGuo (8-oxodG), in both nuclear and mitochondrial DNA, and 8-oxoGuo in RNA. However, significant quantities of tissue are needed, limiting its use in human biomonitoring studies. In contrast, the comet assay requires much less material, and as little as 5 μL of blood may be used, offering a minimally invasive means of assessing oxidative stress in vivo , but this is restricted to nuclear DNA damage only. Urine is an ideal matrix in which to non-invasively study nucleic acid-derived biomarkers of oxidative stress, and considerable progress has been made towards robustly validating these measurements, not least through the efforts of the European Standards Committee on Urinary (DNA) Lesion Analysis. For urine, LC-MS/MS is considered the gold standard approach, and although there have been improvements to the ELISA methodology, this is largely limited to 8-oxodG. Emerging DNA adductomics approaches, which either comprehensively assess the totality of adducts in DNA, or map DNA damage across the nuclear and mitochondrial genomes, offer the potential to considerably advance our understanding of the mechanistic role of oxidatively damaged nucleic acids in disease.

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“…After that, an adductome map of urine from a patient under mechanical ventilation in an intensive care unit was compared to the adductome map of one healthy subject. More putative adducts were detected and at a higher intensity in the urine of a patient compared to the healthy individual [116].…”

Section: Extension Of Dna Adductomics Approach To the Emerging Fiementioning

confidence: 99%

Emerging Technologies in Mass Spectrometry-Based DNA Adductomics

Guo

Turesky

2019

High-Throughput

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The measurement of DNA adducts, the covalent modifications of DNA upon the exposure to the environmental and dietary genotoxicants and endogenously produced electrophiles, provides molecular evidence for DNA damage. With the recent improvements in the sensitivity and scanning speed of mass spectrometry (MS) instrumentation, particularly high-resolution MS, it is now feasible to screen for the totality of DNA damage in the human genome through DNA adductomics approaches. Several MS platforms have been used in DNA adductomic analysis, each of which has its strengths and limitations. The loss of 2′-deoxyribose from the modified nucleoside upon collision-induced dissociation is the main transition feature utilized in the screening of DNA adducts. Several advanced data-dependent and data-independent scanning techniques originated from proteomics and metabolomics have been tailored for DNA adductomics. The field of DNA adductomics is an emerging technology in human exposure assessment. As the analytical technology matures and bioinformatics tools become available for analysis of the MS data, DNA adductomics can advance our understanding about the role of chemical exposures in DNA damage and disease risk.

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Urinary DNA adductomics – A novel approach for exposomics

Cited by 34 publications

References 58 publications

New horizons of DNA adductome for exploring environmental causes of cancer

New horizons of DNA adductome for exploring environmental causes of cancer

Biomarkers of nucleic acid oxidation – A summary state-of-the-art

Emerging Technologies in Mass Spectrometry-Based DNA Adductomics

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