| Project/Area Number |
15406027
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 海外学術 |
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| Research Field |
Hygiene
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| Research Institution | Mie University |
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Principal Investigator |
KAWANISHI Shosuke Mie Univeristy, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (10025637)
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| Co-Investigator(Kenkyū-buntansha) |
MURATA Mariko Mie University, Faculty of Medicine, Lecture, 大学院・医学系研究科, 講師 (10171141)
OIKAWA Shinji Mie University, Faculty of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (10277006)
HIRAKU Yusuke Mie University, Faculty of Medicine, Lecture, 大学院・医学系研究科, 講師 (30324510)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2005: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2004: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2003: ¥4,900,000 (Direct Cost: ¥4,900,000)
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| Keywords | Opisthorchis viverrini / cholangiocarcinoma / 8-nitroguanine / infection / inflammation / reactive nitrogen species / inducible NO synthase / carcinogenesis / 8-oxodG / 8-nitroG / NO / ニトロチロシン / ヒストン |
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| Research Abstract |
Infection with the liver fluke Opisthorchis viverrini (OV) is a major risk factor of cholangiocarcinoma especially in north-eastern region of Thailand. Chronic inflammation mediated by infection is an important factor causing cancer. Reactive nitrogen species are generated under inflammatory conditions, and react with guanine to form 8-nitroguanine, a mutagenic nitrative DNA lesion, which may contribute to infection-related carcinogenesis. We produced specific anti-8-nitroguanine antibody, and we firstly demonstrated that 8-nitroguanine was formed in bile duct epithelium of OV-infected hamsters in association with carcinogenesis (BBRC 2003, Nitric Oxide 2004, Carcinogenesis 2004). An antihelminthic drug almost completely diminished iNOS-dependent DNA damage in bile duct epithelium (Int.J.Cancer in press). We carried out a molecular epidemiological study in patients with intrahepatic cholangiocarcinoma. It is noteworthy that 8-nitroguanine formation in surgical specimens of cholangiocar
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cinoma patients was significantly correlated with tumor invasion, suggesting that DNA damage participates in not only initiation and promotion but also tumor progression (World J.Gastroenterol. 2005). We demonstrated that OV antigen induced inflammatory responses via TLR2-dependent pathway in a macrophage cell line (Int.J.Parasitol. 2005). Our international molecular epidemiological study has provided an insight into molecular mechanisms of a wide variety of inflammation-related carcinogenesis. We also investigated DNA damage in patients with various infectious diseases. 8-Nitroguanine was formed in patients with Helicobacter pylori-induced gastritis (BBRC 2004), chronic hepatitis C (J.Hepatol. 2005) and oral premalignant lesions (Cancer Sci. 2005, Nitric Oxide 2006). We showed that 8-nitroguanine was formed in colon epithelium of the mouse model of inflammatory bowel diseases (Cancer Sci. 2005). In these studies, we found that 8-nitroguanine is formed at the sites of carcinogenesis regardless of etiology, and proposed the possibility that 8-nitroguanine could be a promising biomarker to evaluate the risk and prognosis of inflammation-related carcinogenesis. Less
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