Related Experiment Video

Updated: Jan 11, 2026

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
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Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

Published on: August 5, 2022

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Persistent interferon signaling and clonal expansion mark early events in DNA methylation damage-induced liver cancer

Lee J Pribyl1, Jennifer E Kay2, Joshua J Corrigan1

  • 1Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

Biorxiv : the Preprint Server for Biology
|November 19, 2025
PubMed

Insights

N-Nitrosodimethylamine (NDMA) exposure causes DNA damage and triggers a persistent interferon response, leading to liver cancer in mice. MGMT deficiency amplifies these effects, highlighting potential biomarkers for mitigation.

Area of Science:

  • Toxicology
  • Carcinogenesis
  • Molecular Biology

Background:

  • N-Nitrosodimethylamine (NDMA) is a probable human carcinogen.
  • NDMA induces DNA damage, specifically O6-methylguanine lesions.
  • O6-methylguanine methyltransferase (MGMT) repairs these lesions.

Purpose of the Study:

  • To elucidate mechanisms of NDMA-induced liver cancer progression.
  • To analyze phenomic, transcriptomic, and phosphoproteomic changes in response to NDMA.
  • To compare responses between wild-type and MGMT-deficient mice.

Main Methods:

  • Longitudinal analyses of phenomic, transcriptomic, and phosphoproteomic data.
  • Exposure of wild-type and MGMT-deficient mice to NDMA.
  • Spatial transcriptomics for detailed pathway analysis.

Main Results:

  • Amplified molecular responses observed in MGMT-deficient mice.
  • Early detection of DNA damage response pathways.
  • Persistent interferon response correlated with clonal expansion and tumorigenesis.
  • Spatial transcriptomics revealed pathway alterations favoring tumor development.

Conclusions:

  • Acute early-life NDMA exposure triggers a cascade of molecular events leading to liver cancer.
  • Chronic interferon signaling is a key pathway in NDMA-induced oncogenesis.
  • The study identifies potential predictive biomarkers and mitigation strategies for NDMA-induced liver cancer.

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