Crosstalk between DNA Damage and Inflammation in the Multiple Steps of Carcinogenesis

Our plain-English summary of Crosstalk between DNA Damage and Inflammation in the Multiple Steps of Carcinogenesis, by S. Kawanishi, S. Ohnishi, N. Ma, et al (International Journal of Molecular Sciences, 2017).

The study

• Authors: S. Kawanishi, S. Ohnishi, N. Ma, Y. Hiraku, M. Murata
• Journal: International Journal of Molecular Sciences
• Published: 2017;18(8)
• Type of article: Review
• Cited by: 205 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Inflammation can be induced by chronic infection, inflammatory diseases and physicochemical factors. Chronic inflammation is estimated to contribute to approximately 25% of human cancers. Under inflammatory conditions, inflammatory and epithelial cells release reactive oxygen (ROS) and nitrogen species (RNS), which are capable of causing DNA damage, including the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-nitroguanine. We reported that 8-nitroguanine was clearly formed at the sites of cancer induced by infectious agents including Helicobacter pylori, inflammatory diseases including Barrett's esophagus, and physicochemical factors including asbestos. DNA damage can lead to mutations and genomic instability if not properly repaired. Moreover, DNA damage response can also induce high mobility group box 1-generating inflammatory microenvironment, which is characterized by hypoxia. Hypoxia induces hypoxia-inducible factor and inducible nitric oxide synthase (iNOS), which increases the levels of intracellular RNS and ROS, resulting DNA damage in progression with poor prognosis. Furthermore, tumor-producing inflammation can induce nuclear factor-κB, resulting in iNOS-dependent DNA damage. Therefore, crosstalk between DNA damage and inflammation may play important roles in cancer development. A proposed mechanism for the crosstalk may explain why aspirin decreases the long-term risk of cancer mortality.

In plain English

This article was a review, not a new study. The authors summarized research, much of it their own earlier work, on how long-lasting inflammation may damage DNA and contribute to cancer. They described how inflamed tissues release reactive oxygen and nitrogen molecules that can form DNA lesions called 8-nitroguanine and 8-oxodG. They reviewed earlier findings that 8-nitroguanine formed at cancer sites linked to infections, inflammatory diseases, and particles such as asbestos, which they listed with the mesothelium and lung. On asbestos, they reported earlier work that found 8-nitroguanine in bronchial lining cells of asbestos-exposed mice but not significantly in control mice. They also reported that in humans, 8-nitroguanine formation was associated with asbestos contents in lung tissue. They wrote that the precise mechanisms of asbestos-induced cancer have not been well understood. The authors concluded that crosstalk between DNA damage and inflammation may play important roles in cancer development. They proposed a possible mechanism for the reported reduction in long-term cancer mortality with aspirin. They noted that their account focused only on two signaling pathways, NF-κB and STAT3.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review, mainly of the authors' own earlier laboratory, animal and clinical-specimen studies; no new data
• Who was studied: No new population. The earlier studies reviewed used human clinical specimens, animal models (including asbestos-exposed mice) and human cell lines.
• Exposure: Causes of chronic inflammation, including infectious agents, inflammatory diseases and particulate matters such as asbestos, carbon nanotubes and carbon black. The article text does not specify asbestos fiber types.
• Main results:
  • In an earlier study of asbestos-exposed mice, 8-nitroguanine formed in the nucleus of bronchial epithelial cells. Its formation was not significantly observed in control mice.
  • In earlier human work, 8-nitroguanine formation was associated with asbestos contents in lung tissues.
  • The review's table listed asbestos as a causative factor, with the mesothelium and lung as the cancer sites where 8-nitroguanine accumulated.
  • The authors stated that the precise mechanisms of asbestos-induced carcinogenesis were not well understood. They wrote that the mechanisms appear to involve tissue irritation, disruption of cell division, and iron-catalyzed reactive oxygen species causing DNA damage.
  • In the authors' earlier cell work, multi-walled carbon nanotubes taken up by A549 human lung epithelial cells led to iNOS expression and 8-nitroguanine formation.
• The authors' conclusion: The authors concluded that crosstalk between DNA damage and inflammation may play important roles in cancer development. They proposed that aspirin's inhibition of COX-2 is a possible mechanism for its reported reduction of long-term cancer mortality.
• Limitations the authors state:
  • The proposed mechanism focused only on the NF-κB and STAT3 pathways, although other signals may also play a role in carcinogenesis.

Topics

Medical terms in this study, explained in our Lexicon: Inflammation, Carcinogenesis, Chronic Inflammation, 8-Nitroguanine, High Mobility Group Box 1 (HMGB1), Hypoxia, Inducible Nitric Oxide Synthase (iNOS), Prognosis.

Related studies

• Role of nitrative and oxidative DNA damage in inflammation-related carcinogenesis — M. Murata, R. Thanan, et al. (2012)
• The role of iNOS-mediated DNA damage in infection- and asbestos-induced carcinogenesis — Y. Hiraku, S. Kawanishi, et al. (2010)
• Inflammation and cancer — M. Murata (2018)
• The Potential Protective Effects of Polyphenols in Asbestos-Mediated Inflammation and Carcinogenesis of Mesothelium — M. Benvenuto, R. Mattera, et al. (2016)
• Formation of the nitrative DNA lesion 8-nitroguanine is associated with asbestos contents in human lung tissues: a pilot study — Y. Hiraku, K. Sakai, et al. (2014)
• 8-hydroxy-2' -deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis — A. Valavanidis, T. Vlachogianni, et al. (2009)

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