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In our study, we obtained biopsy and surgical specimens of nasopharyngeal tissues from NPC patients in southern China, and performed double immunofluorescent staining to examine the formation of 8\u2010nitroguanine, a nitrative DNA lesion and 8\u2010oxo\u20107,8\u2010dihydro\u20102\u2032\u2010deoxyguanosine, an oxidative DNA lesion, in these specimens. Strong DNA lesions were observed in cancer cells and inflammatory cells in stroma of NPC patients. Intensive immunoreactivity of iNOS was detected in the cytoplasm of 8\u2010nitroguanine\u2010positive cancer cells. DNA lesions and iNOS expression were also observed in epithelial cells of EBV\u2010positive patients with chronic nasopharyngitis, although their intensities were significantly weaker than those in NPC patients. In EBV\u2010negative subjects, no or little DNA lesions and iNOS expression were observed. EGFR and phosphorylated STAT3 were strongly expressed in cancer cells of NPC patients, but NF\u2010\u03baB was not expressed, suggesting that STAT3\u2010dependent mechanism is important for NPC carcinogenesis. IL\u20106 was expressed mainly in inflammatory cells of nasopharyngeal tissues of EBV\u2010infected patients. EBV\u2010encoded RNAs (EBERs) and latent membrane protein 1 (LMP1) were detected in cancer cells from all EBV\u2010infected patients. <jats:italic>In vitro<\/jats:italic> cell system, nuclear accumulation of EGFR was observed in LMP1\u2010expressing cells, and IL\u20106 induced phosphorylated STAT3 and iNOS. These data suggest that nuclear accumulation of EGFR and STAT3 activation byIL\u20106 play the key role in iNOS expression and resultant DNA damage, leading to EBV\u2010mediated NPC. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.23415","type":"journal-article","created":{"date-parts":[[2008,2,28]],"date-time":"2008-02-28T21:20:39Z","timestamp":1204233639000},"page":"2517-2525","source":"Crossref","is-referenced-by-count":77,"title":["Reactive nitrogen species\u2010dependent DNA damage in EBV\u2010associated nasopharyngeal carcinoma: The relation to STAT3 activation and EGFR expression"],"prefix":"10.1002","volume":"122","author":[{"given":"Ning","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiko","family":"Kawanishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Hiraku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Murata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang\u2010Wu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanjiao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dian\u2010Zhong","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Guang","family":"Mo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Fukui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shosuke","family":"Kawanishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,2,28]]},"reference":[{"key":"e_1_2_5_2_2","first-page":"125","article-title":"Nasopharyngeal carcinoma:an epidemiological approach to carcinogenesis","volume":"33","author":"Jeannel D","year":"1999","journal-title":"Cancer Surv"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2273.2001.00449.x"},{"key":"e_1_2_5_4_2","series-title":"Epstein\u2010Barr virus. 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