Pinlaor Somchai, Yongvanit Puangrat, Hiraku Yusuke, Ma Ning, Semba Reiji, Oikawa Shinji, Murata Mariko, Sripa Banchob, Sithithaworn Paiboon, Kawanishi Shosuke
Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
Biochem Biophys Res Commun. 2003 Sep 26;309(3):567-71. doi: 10.1016/j.bbrc.2003.08.039.
Nucleic acid damage by reactive nitrogen and oxygen species may contribute to the carcinogenesis associated with chronic infection and inflammation. We examined 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation and nitric oxide (NO) production in hamsters infected with Opisthorchis viverrini (OV). Formation of 8-nitroguanine was assessed immunohistochemically with an antibody specific for 8-nitroguanine. 8-nitroguanine formation was found mainly in the cytoplasm and slightly in the nucleus of inflammatory cells and epithelial lining of bile duct at inflammatory areas in the liver. 8-nitroguanine immunoreactivity reached the highest intensity on day 30. A time profile of 8-nitroguanine formation was closely associated with that of plasma nitrate/nitrite. HPLC with an electrochemical detector revealed that the amount of 8-oxodG in the liver reached the maximal level on day 21. The mechanisms of 8-oxodG and 8-nitroguanine formation via O2*- and NO production triggered by OV infection were discussed in relation to cholangiocarcinoma development.
活性氮和氧物种造成的核酸损伤可能与慢性感染和炎症相关的致癌作用有关。我们检测了感染华支睾吸虫(OV)的仓鼠体内8-硝基鸟嘌呤和8-氧代-7,8-二氢-2'-脱氧鸟苷(8-氧代脱氧鸟苷,8-oxodG)的形成以及一氧化氮(NO)的产生。使用针对8-硝基鸟嘌呤的特异性抗体通过免疫组织化学方法评估8-硝基鸟嘌呤的形成。发现8-硝基鸟嘌呤的形成主要在肝脏炎症区域的炎性细胞胞质中,在胆管上皮衬里中也有少量,在细胞核中则较少。8-硝基鸟嘌呤免疫反应性在第30天达到最高强度。8-硝基鸟嘌呤形成的时间曲线与血浆硝酸盐/亚硝酸盐的时间曲线密切相关。采用电化学检测器的高效液相色谱法显示,肝脏中8-氧代脱氧鸟苷的量在第21天达到最高水平。讨论了OV感染引发的通过超氧阴离子(O2*)和NO产生导致8-氧代脱氧鸟苷和8-硝基鸟嘌呤形成的机制与胆管癌发生发展的关系。