Crosstalk between DNA Damage and Inflammation in the Multiple Steps of Carcinogenesis
AbstractInflammation 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. View Full-Text
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Kawanishi, S.; Ohnishi, S.; Ma, N.; Hiraku, Y.; Murata, M. Crosstalk between DNA Damage and Inflammation in the Multiple Steps of Carcinogenesis. Int. J. Mol. Sci. 2017, 18, 1808.
Kawanishi S, Ohnishi S, Ma N, Hiraku Y, Murata M. Crosstalk between DNA Damage and Inflammation in the Multiple Steps of Carcinogenesis. International Journal of Molecular Sciences. 2017; 18(8):1808.Chicago/Turabian Style
Kawanishi, Shosuke; Ohnishi, Shiho; Ma, Ning; Hiraku, Yusuke; Murata, Mariko. 2017. "Crosstalk between DNA Damage and Inflammation in the Multiple Steps of Carcinogenesis." Int. J. Mol. Sci. 18, no. 8: 1808.
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