The role of iNOS-mediated DNA damage in infection- and asbestos-induced carcinogenesis

Our plain-English summary of The role of iNOS-mediated DNA damage in infection- and asbestos-induced carcinogenesis, by Y. Hiraku, S. Kawanishi, T. Ichinose, et al (Annals of the New York Academy of Sciences, 2010).

The study

• Authors: Y. Hiraku, S. Kawanishi, T. Ichinose, M. Murata
• Journal: Annals of the New York Academy of Sciences
• Published: 2010;1203:15-22
• Type of article: Review
• Cited by: 44 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Chronic inflammation contributes to a substantial part of environmental carcinogenesis. Various infectious diseases and physical, chemical, and immunological factors participate in inflammation-related carcinogenesis. Under inflammatory conditions, reactive oxygen and nitrogen species are generated from inflammatory and epithelial cells, and resulting DNA damage may participate in carcinogenesis. 8-Nitroguanine is a mutagenic DNA lesion formed during chronic inflammation. We performed immunohistochemical analysis, and demonstrated that 8-nitroguanine was formed at the sites of carcinogenesis in animal models and patients with various cancer-prone infectious and inflammatory diseases, caused by parasites, viruses, and asbestos exposure. In asbestos-exposed mice, 8-nitroguanine was formed in bronchial epithelial cells, and it is noteworthy that crocidolite induced significantly more intense 8-nitroguanine formation than chrysotile, inconsistent with their carcinogenic potentials. On the basis of these findings, we have proposed that 8-nitroguanine could be a potential biomarker to evaluate the risk of inflammation-related carcinogenesis.

In plain English

This article was a review by the authors of their own earlier research on 8-nitroguanine, a type of DNA damage that can form during long-lasting inflammation. It covered their work in hamsters infected with a liver fluke and in tissue samples from patients with infections linked to cancer (Helicobacter pylori, hepatitis C virus, human papillomavirus and Epstein-Barr virus). It also described an experiment in which male ICR mice had chrysotile or crocidolite asbestos (0.05 mg per dose) placed directly into the windpipe four times at weekly intervals. The DNA damage was seen mainly in cells lining the airways (bronchial epithelium). Compared with control mice, staining intensity was 1.43 times the control value in chrysotile-exposed mice, a difference that was not statistically significant, and 3.15 times the control value in crocidolite-exposed mice, which was significant. Crocidolite produced significantly more staining than chrysotile. The experiment measured DNA damage, not cancer, and the article did not say how many mice were used. The authors proposed that 8-nitroguanine could be a potential biomarker for judging the risk of inflammation-related cancer.

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 studies, including a mouse experiment on asbestos-exposed lungs (animal experiment with immunohistochemical staining)
• Who was studied: Male ICR mice, 6 weeks of age, plus control mice given the vehicle alone. The number of mice is not stated. The review also covered the authors' earlier work in hamsters and in patient biopsy and surgical specimens.
• Exposure: Chrysotile or crocidolite (UICC standard reference samples), 0.05 mg per intratracheal instillation, repeated 4 times at weekly intervals. Lungs were taken one day after the last instillation. Controls received saline with 0.05% Tween 80.
• Main results:
  • 8-nitroguanine formation was mainly observed in bronchial epithelial cells of asbestos-exposed mice, with little or none in control mice
  • In chrysotile-exposed mice, staining intensity per unit area of bronchial epithelium was non-significantly increased: 1.43 plus or minus 0.14-fold the control value, P = 0.127. Control mice were 1.00 plus or minus 0.14-fold.
  • In crocidolite-exposed mice, staining intensity was significantly increased: 3.15 plus or minus 0.53-fold the control value, P less than 0.001
  • Staining intensity in crocidolite-exposed mice was significantly higher than in chrysotile-exposed mice (P less than 0.01)
  • Crocidolite also induced iNOS expression and nuclear translocation of the transcription factor NF-kappaB to a significantly greater extent than chrysotile
• The authors' conclusion: The authors concluded that 8-nitroguanine formation may take part in inflammation-related carcinogenesis as a common mechanism and could be used as a potential biomarker for evaluating cancer risk

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenesis, Chronic Inflammation, Inflammation, 8-Nitroguanine, Asbestos Exposure, Crocidolite, Chrysotile, Carcinogenic.

Related studies

• Crosstalk between DNA Damage and Inflammation in the Multiple Steps of Carcinogenesis — S. Kawanishi, S. Ohnishi, et al. (2017)
• Beta-carotene metabolites enhance inflammation-induced oxidative DNA damage in lung epithelial cells — Y.G. van Helden, J. Keijer, et al. (2009)
• 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)
• Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis — H. Ohshima, H. Bartsch (1994)
• Role of nitrative and oxidative DNA damage in inflammation-related carcinogenesis — M. Murata, R. Thanan, et al. (2012)
• Asbestos exposure affects poly(ADP-ribose) polymerase-1 activity: role in asbestos-induced carcinogenesis — M. Tomasetti, M. Amati, et al. (2011)

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