Molecular epidemiology study on carcinogenic mechanism of Epstein-Barr-associated nasopharyngeal carcinoma and modification by environmental factors in southern China

爱泼斯坦-巴尔病毒感染的鼻咽癌是中国南部的一个重要健康问题。我们采集了中国南部地区鼻咽癌患者的血清和鼻咽组织活检标本。我们进行了双重免疫荧光染色，以检测这些标本中硝化型和氧化型DNA损伤(8-硝基-7，8-二氢-2‘-脱氧鸟苷(8-oxodG))的形成。在鼻咽癌患者的癌细胞和炎性细胞中可观察到DNA损伤。INOS在癌细胞胞浆内呈强阳性反应。IL-6诱导的EGFR和STAT3的核积聚可能在iNOS表达和DNA损伤中起关键作用，从而导致EBV介导的鼻咽癌。鼻咽癌患者血清8-oxodG水平明显高于对照组。在所有6个鼻咽癌细胞系和大多数原代鼻咽癌组织中都检测到RAS相关糖尿病相关基因(RRAD)的启动子高甲基化。这些发现可能为预防鼻咽癌的发展提供一种策略。

Epstein-Barr virus-infected nasopharyngeal carcinoma (NPC) is an important health problem in southern China. We obtained serum and biopsy specimens of nasopharyngeal tissues from NPC patients in southern China. We performed double immunofluorescent staining to examine the formation of nitrative and oxidative DNA lesions (8-nitroguanine, and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG)) in these specimens. DNA lesions were observed in cancer cells and inflammatory cells of NPC patients. Intensive immunoreactivity of iNOS was detected in the cytoplasm of cancer cells. Nuclear accumulation of EGFR and STAT3 activation by IL-6 may play the key role in iNOS expression and resultant DNA damage, leading to EBV-mediated NPC. The serum level of 8-oxodG in the NPC patients was significantly higher than that in the control. Promoter hypermethylation of Ras-related associated with diabetes (RRAD) was detected in all six NPC cell lines and most of primary NPC tissues. These findings may provide a strategy for preventing the development of NPC.