臨牀消化器内科 Vol.20 No.4(1-3)


特集名 肝と酸化ストレス
題名 酸化ストレスの基礎 (3) 酸化・ニトロ化ストレスとDNA傷害
発刊年月 2005年 04月
著者 川西 正祐 三重大学医学部衛生学教室
著者 平工 雄介 三重大学医学部衛生学教室
【 要旨 】 近年,慢性感染などに伴う炎症の発がんへの関与が注目を集めている.感染・炎症などによる発がんにおいては,炎症反応に関連した細胞増殖刺激およびアポトーシスの抑制に加えて,活性酸素種および活性窒素種によるDNA損傷が重要な役割を果たすと考えられる.われわれはDNAのグアニン残基のニトロ化により8-ニトログアニンが,発がんが起こりうる部位に発がんに先駆けて生成され,炎症関連発がんリスクを評価する新規バイオマーカーとして応用できる可能性を示した.本稿では,タイ肝吸虫感染動物モデルおよびHelicobacter pyloriやC型肝炎感染患者における8-ニトログアニンの発がんにおける役割とその意義について概説する.
Theme Oxidative Stress and the Liver
Title Oxidative and Nitrative Stress-Mediated DNA Damage
Author Shosuke Kawanishi Department of Environmental and Molecular Medicine, Mie University School of Medicine
Author Yusuke Hiraku Department of Environmental and Molecular Medicine, Mie University School of Medicine
[ Summary ] Recently, chronic inflammation, induced by infection, has been postulated to be a risk factor for various forms of cancer. Reactive oxygen and nitrogen species are considered to play a key role in inflammation-mediated carcinogenesis. We examined 8-nitroguanine and 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-oxodG) formation in the liver of hamsters infected with Opisthorchis viverrini (O. viverrini), a liver fluke causing intrahepatic cholangiocarcionoma. Notably, a double immunofluorescence study revealed that formation of 8-nitroguanine and 8-oxodG increased in the epithelium of bile ducts depending on the frequency of O. viverrini infection. In gastritis patients with Helicobacter pylori (H. pylori) infection, the level of 8-nitroguanine in the gastric gland epithelium was significantly higher than in those without H. pylori infection. Interestingly, H. pylori eradication attenuated 8-nitroguanine formation in the gastric epithelium. Moreover, in patients with hepatitis C viral infection, 8-nitroguanine formation was observed in hepatocytes. These results suggest that 8-nitroguanine can be utilized as a promising biomarker to evaluate the cancer risk and efficacy of treatment for inflammation-related diseases. Here in we discuss the role of 8-nitroguanine in inflammation-mediated carcinogenesis.
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