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8-oxo-dGTP curbs tumor development via S phase arrest and AIF-mediated apoptosis

Jin Li1, He Zhang2, Zhen-He Wang1

  • 1The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, PR China.

Free Radical Biology & Medicine
|January 14, 2023
PubMed

Insights

Oxidative stress impacts nucleic acids. This study reveals 8-oxo-dGTP suppresses tumors by damaging DNA, while 8-oxoGTP promotes tumor development, highlighting distinct roles in cancer.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Oxidative Stress Biology

Background:

  • Oxidative stress damages cellular nucleic acids.
  • The roles of oxidized nucleotide triphosphates, 8-oxo-dGTP and 8-oxoGTP, in DNA/RNA oxidation and tumor development are unclear.

Purpose of the Study:

  • To investigate the distinct effects of 8-oxo-dGTP and 8-oxoGTP on tumor development and nucleic acid oxidation.

Main Methods:

  • Intravenous administration of 8-oxo-dGTP and 8-oxoGTP to wild-type and MTH1-knockout mice.
  • Tumor incidence assessment in various mouse models, including xenograft and C57/6J-ApcMin/Nju.
  • Analysis of DNA damage (8-oxo-dG content, strand breaks), cell cycle progression, and apoptosis.

Main Results:

  • 8-oxoGTP administration increased tumor incidence, particularly in MTH1-knockout mice.
  • 8-oxo-dGTP administration reduced tumor development irrespective of genotype.
  • 8-oxo-dGTP induced DNA damage, S-phase cell cycle arrest, and apoptosis, leading to tumor suppression.

Conclusions:

  • 8-oxo-dGTP and 8-oxoGTP play distinct and opposing roles in tumor development.
  • 8-oxo-dGTP exhibits tumor-suppressive properties through DNA damage induction.
  • 8-oxoGTP may act as a tumor promoter, especially under conditions of impaired nucleotide pool regulation.
Keywords:
8-oxo-dGTP8-oxoGTPMTH1tumor inhibitiontumorigenesis

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