Role of nitrative and oxidative DNA damage in inflammation-related carcinogenesis

Our plain-English summary of Role of nitrative and oxidative DNA damage in inflammation-related carcinogenesis, by M. Murata, R. Thanan, N. Ma, et al (Journal of Biomedicine & Biotechnology, 2012).

The study

• Authors: M. Murata, R. Thanan, N. Ma, S. Kawanishi
• Journal: Journal of Biomedicine & Biotechnology
• Published: 2012;2012:623019
• Type of article: Review
• Cited by: 158 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Chronic inflammation induced by biological, chemical, and physical factors has been found to be associated with the increased risk of cancer in various organs. We revealed that infectious agents including liver fluke, Helicobacter pylori, and human papilloma virus and noninfectious agents such as asbestos fiber induced iNOS-dependent formation of 8-nitroguanine and 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-oxodG) in cancer tissues and precancerous regions. Our results with the colocalization of phosphorylated ATM and γ-H2AX with 8-oxodG and 8-nitroguanine in inflammation-related cancer tissues suggest that DNA base damage leads to double-stranded breaks. It is interesting from the aspect of genetic instability. We also demonstrated IL-6-modulated iNOS expression via STAT3 and EGFR in Epstein-Barr-virus-associated nasopharyngeal carcinoma and found promoter hypermethylation in several tumor suppressor genes. Such epigenetic alteration may occur by controlling the DNA methylation through IL-6-mediated JAK/STAT3 pathways. Collectively, 8-nitroguanine would be a useful biomarker for predicting the risk of inflammation-related cancers.

In plain English

This article was a review in which the authors summarized their own earlier research on two kinds of DNA damage that inflammation can produce: 8-nitroguanine (nitrative damage) and 8-oxodG (oxidative damage). This work used animal models and clinical samples. It covered infectious agents including liver fluke, Helicobacter pylori and human papilloma virus, and noninfectious agents such as asbestos fiber. For asbestos, the review described an earlier study by the authors' group in which mice were given asbestos fibers, including crocidolite and chrysotile, into the windpipe. 8-Nitroguanine was detected significantly more in bronchial lining cells of asbestos-exposed groups than in the untreated group. 8-Nitroguanine and two inflammation-related molecules (iNOS and NF-κB) were significantly higher in the crocidolite-exposed group than in the chrysotile-exposed group. The review gave no doses, animal numbers, P values or other numerical statistical results for that study. The authors concluded that nitrative DNA damage could be one of the mechanisms behind the difference in cancer-causing potential between crocidolite and chrysotile. They also concluded that 8-nitroguanine would be a useful biomarker for predicting the risk of inflammation-related cancers.

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: Review of the authors' own previous studies (animal experiments and clinical tissue studies)
• Who was studied: Animal models and clinical samples from the authors' earlier studies; for asbestos, the lungs of mice
• Exposure: For the asbestos part: asbestos fibers, including crocidolite and chrysotile, given to mice intratracheally (into the windpipe). The review also covered infectious agents and inflammatory diseases.
• Main results:
  • In the authors' earlier studies, infectious agents (liver fluke, Helicobacter pylori, human papilloma virus) and noninfectious agents such as asbestos fiber induced formation of 8-nitroguanine and 8-oxodG in cancer tissues and precancerous regions
  • In the mouse study, 8-nitroguanine was detected significantly more in bronchial epithelial cells of asbestos-exposed groups than in the untreated group (no numerical results given in the review)
  • In the mouse study, immunoreactivities of 8-nitroguanine, iNOS and NF-κB were significantly higher in the crocidolite-exposed group than in the chrysotile-exposed group (no numerical results given in the review)
  • The authors proposed 8-nitroguanine as a biomarker for predicting the risk of inflammation-related cancers
• The authors' conclusion: The authors concluded that the formation of nitrative DNA damage could be one of the mechanisms responsible for the difference in carcinogenic potential between crocidolite and chrysotile

Topics

Medical terms in this study, explained in our Lexicon: Inflammation, Carcinogenesis, Chronic Inflammation, 8-Nitroguanine, EGFR, Carcinoma, Tumor Suppressor Gene, Biomarker.

Related studies

• Crosstalk between DNA Damage and Inflammation in the Multiple Steps of Carcinogenesis — S. Kawanishi, S. Ohnishi, et al. (2017)
• Tobacco smoke: involvement of reactive oxygen species and stable free radicals in mechanisms of oxidative damage, carcinogenesis and synergistic effects with other respirable particles — A. Valavanidis, T. Vlachogianni, et al. (2009)
• 8-Hydroxy-2'-deoxyguanosine as a marker of oxidative DNA damage related to occupational and environmental exposures — A. Pilger, H.W. Rüdiger (2006)
• Beta-carotene metabolites enhance inflammation-induced oxidative DNA damage in lung epithelial cells — Y.G. van Helden, J. Keijer, et al. (2009)
• 8-hydroxy-2' -deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis — A. Valavanidis, T. Vlachogianni, et al. (2009)
• Inflammation and cancer — M. Murata (2018)

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