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N2-(1-carboxyethyl)-2′-deoxyguanosine as a genotoxic glycation marker associated with chromatin architectural alterations in oral squamous cell carcinoma
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  • Published: 25 March 2026

N2-(1-carboxyethyl)-2′-deoxyguanosine as a genotoxic glycation marker associated with chromatin architectural alterations in oral squamous cell carcinoma

  • Gulnaz Khan  ORCID: orcid.org/0009-0008-7858-17371,2,
  • Rizwana Sanaullah Waraich2,
  • Hurtamina Khan3 &
  • …
  • Rifat Zubair Ahmed  ORCID: orcid.org/0000-0002-5530-13831 

Scientific Reports , Article number:  (2026) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Biochemistry
  • Biomarkers
  • Cancer
  • Genetics
  • Molecular biology
  • Oncology

Abstract

Oral cancer is a major public health concern in South Asia, particularly in Pakistan, India, and Bangladesh, largely due to the widespread use of smokeless tobacco (SLT) products. The World Health Organization (WHO) classifies SLT as a Group 1 carcinogen. These products contain glycotoxins, such as methylglyoxal (MGO) that is well-known to cause genotoxicity by reacting with DNA. One of the most stable MGO-derived DNA adducts is N2-(1-carboxyethyl)-2′-deoxyguanosine (CEdG), which has been reported to cause DNA damage and genetic instability. However, the role of CEdG in the pathogenesis of oral cancer remains unstudied, and the MGO content in various SLT has not been previously determined. To our knowledge, this study represents one of the first investigations into the abundance of CEdG in oral cancer and its association with chromatin organization, while also quantifying MGO levels in SLT. CEdG was detected using a semi-quantitative in situ immunofluorescence assay and correlated with chromatin computational morphometry to evaluate CEdG-associated alterations in chromatin organization. Using ELISA, we also assessed MGO levels in various SLT, revealing elevated concentrations in commonly used products such as gutka, naswar, and khaini. Our results demonstrated significantly higher levels of CEdG in cancerous nuclei and were strongly correlated with disorganized chromatin texture. Together, these findings suggest that exposure to MGO-rich SLT is associated with CEdG accumulation and subsequent chromatin disorganization, which may be relevant to tobacco-associated oral carcinogenesis.

Data availability

Data are available in supplementary information files.

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Acknowledgements

We sincerely thank Prof. Monika Pischetsrieder (Department of Chemistry and Pharmacy, Food Chemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany) for the kind gift of the N2-(1-carboxyethyl)-2′-deoxyguanosine (CEdG) monoclonal antibody. The CEdG antibody was specially provided for the PhD research project of Gulnaz Khan.

Author information

Authors and Affiliations

  1. Department of Genetics, University of Karachi, Karachi, Pakistan

    Gulnaz Khan & Rifat Zubair Ahmed

  2. Biomedical Research Center, Department of Biomedical and Biological Sciences, Sohail University, Karachi, Pakistan

    Gulnaz Khan & Rizwana Sanaullah Waraich

  3. Department of Head and Neck Surgery, Jinnah Postgraduate Medical Centre / Jinnah Sindh Medical University, Karachi, Pakistan

    Hurtamina Khan

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  1. Gulnaz Khan
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Contributions

GK & RSW designed the study. GK performed the experiments, analyzed the data, and wrote the manuscript. RSW, RZA, HK reviewed and edited the manuscript. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Gulnaz Khan.

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The authors declare no competing interests.

Ethical approval and consent

The study was approved by the Institutional Review Board (IRB), Jinnah Postgraduate Medical Center (JPMC), Jinnah Hospital, Karachi (Ref No. NO.F.2–81/2020-GENL/48723/JPMC), and was conducted in accordance with the ethical principles of the Declaration of Helsinki. Written informed consent was obtained from all participants prior to inclusion in the study.

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Khan, G., Waraich, R.S., Khan, H. et al. N2-(1-carboxyethyl)-2′-deoxyguanosine as a genotoxic glycation marker associated with chromatin architectural alterations in oral squamous cell carcinoma. Sci Rep (2026). https://doi.org/10.1038/s41598-026-45839-w

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  • Received: 06 October 2025

  • Accepted: 23 March 2026

  • Published: 25 March 2026

  • DOI: https://doi.org/10.1038/s41598-026-45839-w

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Keywords

  • N2-(1-carboxyethyl)-2′-deoxyguanosine
  • DNA damage
  • Genetic instability
  • Chromatin organization
  • Oral cancer
  • Smokeless tobacco
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