Endogenous versus Exogenous DNA Adducts: Their Role in Carcinogenesis, Inflammation, Epidemiology, and Risk Assessment

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biomacromolecules: Nucleic Acids".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 3013

Special Issue Editor


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Guest Editor
School of Public Health, Hongqiao International Institute of Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Interests: DNA damage and DNA adducts; genotoxicity; mutagenicity; myeloperoxidase- and neutrophil-mediated metabolism; hydrogen peroxide; hypochlorous acid; oxidative degradation of bilirubin; biomarkers; environmental pollutants

Special Issue Information

Dear Colleagues,

DNA adducts are a form of DNA damage caused by the covalent attachment of a chemical moiety to DNA. If left unrepaired, they can lead to mutations, contributing to the occurrence of cancers. Thus, the formation of DNA adducts is generally accepted as the initiating molecular event in carcinogenesis. The structures of DNA adducts can indicate the chemicals causing the formation of adducts, and the levels of adducts may be associated with the cancer risks. Thus, DNA adducts are biomarkers of both exposure and effects, and can be used in biomonitoring and cancer risk assessment.

Most studies have focused on DNA adducts caused by exogenous chemicals; however, DNA adducts can also be formed endogenously through interactions with reactive molecules (or radicals) generated in the endogenously physiological processes, such as formaldehyde, 4-hydroxy-2-nonenal, and reactive oxygen species (ROS). 8-Oxo-deoxyguanosine, a common product of DNA oxidation by ROS, is an endogenous DNA adduct.

Although they are usually associated with carcinogenesis, DNA adducts also play an important role in other biological processes, such as senescence and inflammation. Inflammation has been known to be a critical contributor to tumor promotion and progression. In the meantime, inflammation can also lead to the production of ROS, thus indirectly inducing the formation of DNA adducts. Therefore, the formation of DNA adducts can trigger diverse biological processes, beyond mutations and carcinogenesis.

Clearly, the formation of DNA adducts is an extremely important biological event, and the related studies will greatly contribute to our understanding of critical biological processes and underlying molecular mechanisms. Meanwhile, as key biomarkers of exposure and effects, DNA adducts can have many applications in the epidemiology and risk assessment of chemicals. In the Special Issue, authors are invited to submit manuscripts to delineate the roles of DNA adducts in various biological processes, in particular in carcinogenesis and inflammation, and to investigate the applications of DNA adducts in epidemiology and risk assessment. In an era of -omics, DNA adductomics is certainly covered in this Special Issue. However, our major focus is on biochemistry and molecular biology (in vitro and in vivo studies); we will not cover clinical and analytical chemical studies. Review articles will also be considered.

Dr. Xinyu Zhang
Guest Editor

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Keywords

  • DNA adducts
  • DNA adductomics
  • mutagenesis
  • carcinogenesis
  • inflammation
  • molecular mechanisms
  • biomarkers
  • biomonitoring
  • risk assessment
  • environmental pollutants

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Published Papers (2 papers)

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Research

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16 pages, 3402 KiB  
Article
Evaluation of the Mechanisms Involved in the Development of Bladder Toxicity following Exposure to Occupational Bladder Cancer Causative Chemicals Using DNA Adductome Analysis
by Shugo Suzuki, Min Gi, Masami Komiya, Asuka Obikane, Arpamas Vachiraarunwong, Masaki Fujioka, Anna Kakehashi, Yukari Totsuka and Hideki Wanibuchi
Biomolecules 2024, 14(1), 36; https://doi.org/10.3390/biom14010036 - 26 Dec 2023
Cited by 5 | Viewed by 1510
Abstract
Occupational exposure to aromatic amines (AAs) is an important risk factor for urinary bladder cancer. This study aimed to evaluate the toxicity of AAs and analyze the carcinogenic mechanisms in rat bladder by comprehensive analysis of DNA adducts (DNA adductome). DNA was extracted [...] Read more.
Occupational exposure to aromatic amines (AAs) is an important risk factor for urinary bladder cancer. This study aimed to evaluate the toxicity of AAs and analyze the carcinogenic mechanisms in rat bladder by comprehensive analysis of DNA adducts (DNA adductome). DNA was extracted from the bladder epithelia of rats treated with AAs, including acetoacet-o-toluidine (AAOT) and o-toluidine (OTD), and adductome analysis was performed. Principal component analysis–discriminant analysis revealed that OTD and AAOT observed in urinary bladder hyperplasia could be clearly separated from the controls and other AAs. After confirming the intensity of each adduct, four adducts were screened as having characteristics of the OTD/AAOT treatment. Comparing with the in-house DNA adduct database, three of four candidates were identified as oxidative DNA adducts, including 8-OH-dG, based on mass fragmentation together with high-resolution accurate mass (HRAM) spectrometry data. Therefore, findings suggested that oxidative stress may be involved in the toxicity of rat bladder epithelium exposed to AAs. Consequently, the administration of apocynin, an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase, in six-week-old rats fed with 0.6% OTD in their diet resulted in simple hyperplastic lesions in the bladder that were suppressed by apocynin. The labeling indices of Ki67, γ-H2AX, and 8-OHdG were significantly decreased in an apocynin concentration-dependent manner. These findings indicate that oxidative stress may have contributed to the development of urinary cancer induced by OTD. Full article
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Review

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20 pages, 802 KiB  
Review
DNA Adductomics: A Narrative Review of Its Development, Applications, and Future
by Mengqiu Cao and Xinyu Zhang
Biomolecules 2024, 14(9), 1173; https://doi.org/10.3390/biom14091173 - 19 Sep 2024
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Abstract
DNA adductomics is the global study of all DNA adducts and was first proposed in 2006 by the Matsuda group. Its development has been greatly credited to the advances in mass spectrometric techniques, particularly tandem and multiple-stage mass spectrometry. In fact, liquid chromatography-mass [...] Read more.
DNA adductomics is the global study of all DNA adducts and was first proposed in 2006 by the Matsuda group. Its development has been greatly credited to the advances in mass spectrometric techniques, particularly tandem and multiple-stage mass spectrometry. In fact, liquid chromatography-mass spectrometry (LC-MS)-based methods are virtually the sole technique with practicality for DNA adductomic studies to date. At present, DNA adductomics is primarily used as a tool to search for DNA adducts, known and unknown, providing evidence for exposure to exogenous genotoxins and/or for the molecular mechanisms of their genotoxicity. Some DNA adducts discovered in this way have the potential to predict cancer risks and/or to be associated with adverse health outcomes. DNA adductomics has been successfully used to identify and determine exogenous carcinogens that may contribute to the etiology of certain cancers, including bacterial genotoxins and an N-nitrosamine. Also using the DNA adductomic approach, multiple DNA adducts have been observed to show age dependence and may serve as aging biomarkers. These achievements highlight the capability and power of DNA adductomics in the studies of medicine, biological science, and environmental science. Nonetheless, DNA adductomics is still in its infancy, and great advances are expected in the future. Full article
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