New horizons of DNA adductome for exploring environmental causes of cancer

Totsuka, Yukari; Watanabe, Masatoshi; Lin, Yingsong

doi:10.1111/cas.14666

Cited by 32 publications

(34 citation statements)

References 34 publications

(66 reference statements)

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“…Similar studies have been conducted in mice, arguing that exposure to various chemical carcinogens does not produce fully unique mutational signatures, but only specific mutational signatures are observed [101]. Both the estimation of mutational signatures by deep sequencing and the direct identification of DNA adducts by mass spectrometry reveal the chemical changes that DNA has undergone, but only a few studies have combined the two methods [102][103][104][105]. It becomes important to understand the state before and after the occurrence of mutation by these two methods based on different principles.…”

Section: Mutational Signature Analysis Combined With Experimental Exposure and Perturbation Of Genetic Backgroundsmentioning

confidence: 78%

Geospatial Assessments of DNA Adducts in the Human Stomach: A Model of Field Cancerization

Iwashita

Ohnishi

Matsushita

et al. 2021

Cancers

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Background: Field cancerization is a popular concept regarding where cancer cells arise in a plane, such as the opened-up gastrointestinal mucosa. The geospatial distribution of DNA adducts, some of which are believed to initiate mutation, may be a clue to understanding the landscape of the preferred occurrence of gastric cancer in the human stomach, such that the occurrence is much more frequent in the lesser curvature than in the greater curvature. Methods: Seven DNA adducts, 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, from different points and zones of the human stomach were semi quantitatively measured by liquid chromatography/tandem mass spectrometry. The differences in the quantity of these DNA adducts from the lesser and greater curvature, the upper, middle and lower third zones, the anterior and posterior wall of the stomach, and the mucosae distant from and near the tumor were compared to determine whether the location preference of cancer in the stomach could be explained by the distribution of these DNA adducts. Comparisons were conducted considering the tumor locations and operation methods. Conclusions: Regarding the DNA adducts investigated, significant differences in quantities and locations in the whole stomach were not noted; thus, these DNA adducts do not explain the preferential occurrence of cancer in particular locations of the human stomach.

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Section: Mutational Signature Analysis Combined With Experimental Exposure and Perturbation Of Genetic Backgroundsmentioning

confidence: 78%

Geospatial Assessments of DNA Adducts in the Human Stomach: A Model of Field Cancerization

Iwashita

Ohnishi

Matsushita

et al. 2021

Cancers

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“…Lastly, a novel approach is needed for meaningful interpretation of the DNA adductome-based exposomes and future DNA adduct maps to improve our understand in cancer etiology and explain the origin of mutational signatures established for various tumor types [98].…”

Section: Discussionmentioning

confidence: 99%

Current and Future Methodology for Quantitation and Site-specific Mapping the Location of DNA Adducts

Boysen¹,

Nookaew²

2021

Preprint

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Formation of DNA adducts is a key event for a genotoxic mode of action and its formation is often use as surrogate for mutation and cancer. Interest in DNA adducts are twofold, first, to demonstrate exposure, and second, to link DNA adduct location to subsequent mutations or altered gene regulation. High chemically specific mass spectrometry methods have been established for DNA adduct quantitation and elegant bio-analytic methods utilizing enzymes, various chemistries, and molecular biology methods to visualize the location of DNA adducts. Traditionally, these highly specific methods cannot be combined, and the results are incomparable. Initially developed for single-molecule DNA sequencing, nanopore-type technologies are expected to enable simultaneous quantitation and location of DNA adducts across the genome. We will briefly summarize the current methodologies for state-of-the-art quantitation of DNA adduct levels and mapping of DNA adducts and describe novel single-molecule DNA sequencing technology that is expected to achieve both measures simultaneously. Emerging technologies are expected to soon provide a comprehensive picture of the exposome and identify gene regions susceptible to DNA adduct formation.

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“…In this approach, the first step is LC-MS-based analysis followed by validation of biological activities and analysis of mutational signatures. The last step is to measure DNA adduct levels in blood or tissue samples (Totsuka et al 2021 ).…”

Section: Relationship Between Dna Adduct and Tumor Occupationmentioning

confidence: 99%

“…Examples of these DNA-damaging carcinogens include mycotoxins, polycyclic aromatic hydrocarbons, forms DNA adducts. Studies that govern the role of mutagens being the associator in the formation of DNA adducts are extensively described (Arlt et al 2005 ; Totsuka et al 2021 ). Also, how these DNA adducts are identified using sophisticated molecular techniques such as gas chromatography, liquid chromatography/mass spectroscopy (LC/MS), and fluorescent methods in the measurement of DNA adducts is an important concept, preventing adduct formation and cellular damage.…”

Section: Introductionmentioning

confidence: 99%

Unboxing the molecular modalities of mutagens in cancer

Kumari

Sharma

Advani

et al. 2021

Environ Sci Pollut Res

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Graphical abstract The etiology of the majority of human cancers is associated with a myriad of environmental causes, including physical, chemical, and biological factors. DNA damage induced by such mutagens is the initial step in the process of carcinogenesis resulting in the accumulation of mutations. Mutational events are considered the major triggers for introducing genetic and epigenetic insults such as DNA crosslinks, single- and double-strand DNA breaks, formation of DNA adducts, mismatched bases, modification in histones, DNA methylation, and microRNA alterations. However, DNA repair mechanisms are devoted to protect the DNA to ensure genetic stability, any aberrations in these calibrated mechanisms provoke cancer occurrence. Comprehensive knowledge of the type of mutagens and carcinogens and the influence of these agents in DNA damage and cancer induction is crucial to develop rational anticancer strategies. This review delineated the molecular mechanism of DNA damage and the repair pathways to provide a deep understanding of the molecular basis of mutagenicity and carcinogenicity. A relationship between DNA adduct formation and cancer incidence has also been summarized. The mechanistic basis of inflammatory response and oxidative damage triggered by mutagens in tumorigenesis has also been highlighted. We elucidated the interesting interplay between DNA damage response and immune system mechanisms. We addressed the current understanding of DNA repair targeted therapies and DNA damaging chemotherapeutic agents for cancer treatment and discussed how antiviral agents, anti-inflammatory drugs, and immunotherapeutic agents combined with traditional approaches lay the foundations for future cancer therapies.

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New horizons of DNA adductome for exploring environmental causes of cancer

Cited by 32 publications

References 34 publications

Geospatial Assessments of DNA Adducts in the Human Stomach: A Model of Field Cancerization

Geospatial Assessments of DNA Adducts in the Human Stomach: A Model of Field Cancerization

Current and Future Methodology for Quantitation and Site-specific Mapping the Location of DNA Adducts

Unboxing the molecular modalities of mutagens in cancer

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