Abstract
Infection and chronic inflammation have been recognized as important factors for carcinogenesis. Under inflammatory conditions, reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated from inflammatory and epithelial cells and result in oxidative and nitrative DNA damage, such as 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-nitroguanine. The DNA damage can cause mutations and has been implicated in the initiation and/or promotion of inflammation-mediated carcinogenesis. It has been estimated that various infectious agents are carcinogenic to humans (IARC group 1), including parasites (Schistosoma haematobium (SH) and Opisthorchis viverrini (OV)), viruses (hepatitis C virus (HCV), human papillomavirus (HPV), and Epstein-Barr virus (EBV)), and bacterium Helicobacter pylori (HP). SH, OV, HCV, HPV, EBV, and HP are important risk factors for bladder cancer, cholangiocarcinoma, hepatocellular carcinoma, cervical cancer, nasopharyngeal carcinoma, and gastric cancer, respectively. We demonstrated that 8-nitroguanine was strongly formed via inducible nitric oxide synthase (iNOS) expression at these cancer sites of patients. Moreover, 8-nitroguanine was formed in Oct3/4-positive stem cells in SH-associated bladder cancer tissues and in Oct3/4- and CD133-positive stem cells in OV-associated cholangiocarcinoma tissues. Therefore, it is considered that oxidative and nitrative DNA damage in stem cells may play a key role in inflammation-related carcinogenesis.
Highlights
DNA Damage in Inflammation-Related CarcinogenesisInfection and chronic inflammation have been recognized as important risk factors for carcinogenesis and malignancies [1,2,3]
Infection and chronic inflammation have been recognized as important factors for carcinogenesis
It has been estimated that various infectious agents are carcinogenic to humans (IARC group 1), including parasites (Schistosoma haematobium (SH) and Opisthorchis viverrini (OV)), viruses (hepatitis C virus (HCV), human papillomavirus (HPV), and EpsteinBarr virus (EBV)), and bacterium Helicobacter pylori (HP)
Summary
Infection and chronic inflammation have been recognized as important risk factors for carcinogenesis and malignancies [1,2,3]. Regarding inflammation-related carcinogenesis without infection, we describe the formation of 8-nitroguanine in lung tissues of mice intratracheally administered asbestos [42], the precise mechanism of nitrative DNA damage remains to be clarified. On the basis of our studies, various pathogenic factors induce inflammatory responses and the production of ROS and RNS from inflammatory and epithelial cells via iNOS expression, which is regulated by transcriptional factors including NF-κB, STAT, and HIF-1α [2, 3]. It is noteworthy that K-ras mutation mediates cell overproliferation and the accumulation of mutagenic DNA lesions, leading to carcinogenesis These findings imply that DNA damage mediated by ROS and RNS may participate in carcinogenesis via activation of protooncogenes and inactivation of tumor suppressor genes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
