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DNA damage in inflammation-related carcinogenesis and cancer stem cells

Shiho Ohnishi1, Ning Ma2, Raynoo Thanan3

  • 1Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka 513-8670, Mie, Japan.

Oxidative Medicine and Cellular Longevity
|January 3, 2014
PubMed

Insights

Infection and inflammation cause DNA damage, leading to cancer. This study shows that 8-nitroguanine in stem cells is key to inflammation-related carcinogenesis, implicating infectious agents in various cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pathology

Background:

  • Infection and chronic inflammation are recognized drivers of carcinogenesis.
  • Inflammatory conditions generate reactive oxygen and nitrogen species (ROS/RNS), causing oxidative and nitrative DNA damage.
  • This DNA damage, including 8-oxodG and 8-nitroguanine, can lead to mutations and promote inflammation-mediated cancers.

Purpose of the Study:

  • To investigate the role of infectious agents in carcinogenesis.
  • To examine the formation of 8-nitroguanine in inflammation-associated cancers.
  • To explore the involvement of stem cells in inflammation-related carcinogenesis.

Main Methods:

  • Analysis of DNA damage markers (8-nitroguanine) in patient cancer tissues.
  • Assessment of inducible nitric oxide synthase (iNOS) expression.
  • Identification of 8-nitroguanine in specific stem cell populations (Oct3/4+, CD133+).

Main Results:

  • Infectious agents like Schistosoma haematobium, Opisthorchis viverrini, HCV, HPV, EBV, and H. pylori are linked to specific cancers.
  • Strong formation of 8-nitroguanine was observed at cancer sites, correlated with iNOS expression.
  • 8-nitroguanine was detected in Oct3/4-positive stem cells in bladder cancer and Oct3/4/CD133-positive stem cells in cholangiocarcinoma.

Conclusions:

  • Oxidative and nitrative DNA damage in stem cells is a critical factor in inflammation-related carcinogenesis.
  • Specific infectious agents are significant risk factors for various human cancers.
  • Targeting DNA damage in stem cells may offer therapeutic strategies for inflammation-driven cancers.

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