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Review
. 2012:2012:623019.
doi: 10.1155/2012/623019. Epub 2012 Jan 26.

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

Mariko Murata  1 , Raynoo Thanan, Ning Ma, Shosuke Kawanishi
Affiliations
Review

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

Mariko Murata et al. J Biomed Biotechnol. 2012.

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.

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Figures

Figure 1
Figure 1
Proposed mechanism of point mutation induced by 8-nitroguanine and 8-oxodG through induction of the G : C → T : A transversion.
Figure 2
Figure 2
8-Nitroguanine in colon epithelium of a patient with active ulcerative colitis.
Figure 3
Figure 3
Colocalization of DDR proteins and DNA lesions. (a) Colocalization of γ-H2AX (green) and 8-nitroguanine (red). (b) Colocalization of phosphorylated ATM (green) and 8-oxodG (red).
Figure 4
Figure 4
Proposed roles of nitrative and oxidative DNA damage in inflammation-related carcinogenesis.
See this image and copyright information in PMC

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