Medical Scientific Research Center, Guangxi Medical University, 530021 Nanning, People's Republic of China.
Med Oncol. 2011 Mar;28(1):377-84. doi: 10.1007/s12032-010-9434-2. Epub 2010 Mar 26.
Currently, there are no satisfactory biomarkers available to screen for nasopharyngeal carcinoma (NPC). Nitric oxide (NO), produced by inducible nitric oxide synthase (iNOS), has been suggested to cause nitrative and oxidative stress, leading to the accumulation of 8-nitroguanine (8-NitroG) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the subsequent transversion mutation of DNA. The aim of this study was to evaluate iNOS expression and the status of nitrative and oxidative stress in NPC. Fifty-nine cases of NPC and 39 cases of chronic nasopharyngitis were investigated to examine the expression of iNOS and the formation of 8-NitroG and 8-OHdG, using double-immunofluorescent staining. The statistical differences in immunoreactivities were analyzed using the Mann-Whitney test. Thirty-six patients from the 57 cases of NPC and 36 healthy controls were investigated to examine the level of serum 8-OHdG, using enzyme-linked immunosorbent assay (ELISA). The statistical differences were analyzed using a t test. Strong DNA lesions were observed in the cancer cells of NPC patients. All cases of NPC were positive for 8-NitroG and 8-OHdG, and 54 (94.7%) were positive for iNOS. NPC samples exhibited significantly more intense staining for 8-NitroG, 8-OHdG and iNOS than those of chronic nasopharyngitis (P < 0.05, respectively). The mean value of serum 8-OHdG in the 36 NPC patients was 0.538 ± 0.336 ng/ml compared to 0.069 ± 0.059 ng/ml for the healthy controls. The difference in the serum levels of 8-OHdG between the NPC patients and controls was statistically significant (P < 0.05). Our present findings suggest that pathological stimulation of nasopharyngeal tissue, caused by bacterial, viral or parasitic inflammation, may lead to nitrative and oxidative DNA lesions, caused by NO. This may contribute to the cause and development of NPC. Thus, 8-NitroG and 8-OHdG could be potential biomarkers for evaluating the risk of NPC. Better understanding of the molecular mechanisms underlying nitrative and oxidative DNA damage may provide clues to molecular targets for new approaches of NPC prevention.
目前，尚无令人满意的生物标志物可用于筛查鼻咽癌（NPC）。诱导型一氧化氮合酶（iNOS）产生的一氧化氮（NO）已被认为会导致硝化和氧化应激，从而导致 8-硝基鸟嘌呤（8-NitroG）和 8-羟基-2'-脱氧鸟苷（8-OHdG）的积累以及随后的 DNA 颠换突变。本研究旨在评估 NPC 中 iNOS 的表达以及硝化和氧化应激的状态。使用双重免疫荧光染色法检测了 59 例 NPC 和 39 例慢性鼻咽炎患者的 iNOS 表达以及 8-NitroG 和 8-OHdG 的形成情况。采用 Mann-Whitney 检验分析免疫反应性的统计学差异。使用酶联免疫吸附试验（ELISA）检测了 36 例 NPC 患者和 36 例健康对照者的血清 8-OHdG 水平，分析了统计学差异。 NPC 患者的癌细胞中观察到强烈的 DNA 损伤。所有 NPC 病例均为 8-NitroG 和 8-OHdG 阳性，54 例（94.7％）为 iNOS 阳性。与慢性鼻咽炎相比，NPC 样本中 8-NitroG、8-OHdG 和 iNOS 的染色强度明显更高（P <0.05）。36 例 NPC 患者的血清 8-OHdG 平均值为 0.538 ± 0.336ng/ml，而健康对照组为 0.069 ± 0.059ng/ml。NPC 患者和对照组之间血清 8-OHdG 水平的差异具有统计学意义（P <0.05）。本研究结果表明，细菌，病毒或寄生虫性炎症引起的鼻咽组织的病理性刺激可能导致由 NO 引起的硝化和氧化 DNA 损伤。这可能有助于 NPC 的病因和发展。因此，8-NitroG 和 8-OHdG 可能是评估 NPC 风险的潜在生物标志物。更好地了解硝化和氧化 DNA 损伤的分子机制可能为 NPC 预防的新方法提供分子靶标线索。
