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Int J Mol Sci. 2017 Aug 19;18(8). pii: E1808. doi: 10.3390/ijms18081808.

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

Author information

1
Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie 513-8670, Japan. kawanisi@suzuka-u.ac.jp.
2
Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie 513-8670, Japan. shiho-o@suzuka-u.ac.jp.
3
Division of Health Science, Graduate School of Health Science, Suzuka University of Medical Science, Suzuka, Mie 513-8670, Japan. maning@suzuka-u.ac.jp.
4
Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan. y-hiraku@doc.medic.mie-u.ac.jp.
5
Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan. mmurata@doc.medic.mie-u.ac.jp.

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.

KEYWORDS:

cancer; inflammation; oxidative stress

PMID:
28825631
PMCID:
PMC5578195
DOI:
10.3390/ijms18081808
[Indexed for MEDLINE]
Free PMC Article

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