Bahar Gideon, Feinmesser Raphael, Shpitzer Thomas, Popovtzer Aaron, Nagler Rafael M
Department of Otorhinolaryngology, Rabin Medical Center, Petah Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Cancer. 2007 Jan 1;109(1):54-9. doi: 10.1002/cncr.22386.
Free radicals such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), which induce oxidative and nitrative stress, are main contributors to oral carcinogenesis. The RNS (nitrosamines: nitrates, NO(3), and nitrites, NO(2)) are also produced by the reaction of ROS and other free radicals with nitric oxide (NO) and are therefore in equilibrium with it.
Whole saliva was collected from a group of 25 consenting oral squamous cell carcinoma (OSCC) patients and from a control group of 25 healthy age- and gender-matched individuals. General and specific salivary antioxidant components, salivary nitrosamines, and oxidatively damaged salivary DNA and proteins were measured.
The findings showed that oxidative and nitrative stress altered the salivary composition in OSCC patients. Analyzed salivary RNS were substantially higher (NO, 60%; NO(2), 190%; NO(3), 93%), whereas all salivary antioxidants were substantially reduced. The 8-hydroxy-deoxyguanosine (8-OHdG) marker (a widely used indicator of DNA oxidation) increased by 65% and the salivary carbonylation level was significantly higher.
The increase in ROS and RNS may have been the event that led to the consumption and reduction of salivary antioxidant systems, thus explaining the oxidative damage to the DNA and proteins, and possibly the promotion of OSCC. The oxidized proteins and DNA found in the saliva of the cancer patients seems to be the first demonstration of a direct link between salivary free radicals, antioxidants, and OSCC. This may be important for better understanding the pathogenesis of the disease and may contribute to its diagnosis and treatment.
活性氧（ROS）和活性氮（RNS）等自由基可诱导氧化应激和硝化应激，是口腔癌发生的主要促成因素。RNS（亚硝胺：硝酸盐、NO₃和亚硝酸盐、NO₂）也是ROS和其他自由基与一氧化氮（NO）反应产生的，因此与之处于平衡状态。
从一组25名同意参与的口腔鳞状细胞癌（OSCC）患者以及25名年龄和性别匹配的健康对照个体中收集全唾液。测量一般和特定的唾液抗氧化成分、唾液亚硝胺以及氧化损伤的唾液DNA和蛋白质。
研究结果表明，氧化应激和硝化应激改变了OSCC患者的唾液成分。分析的唾液RNS显著升高（NO升高60%；NO₂升高190%；NO₃升高93%），而所有唾液抗氧化剂均显著减少。8-羟基脱氧鸟苷（8-OHdG）标志物（一种广泛使用的DNA氧化指标）增加了65%，唾液羰基化水平显著更高。
ROS和RNS的增加可能是导致唾液抗氧化系统消耗和减少的原因，从而解释了对DNA和蛋白质的氧化损伤，以及可能对OSCC的促进作用。癌症患者唾液中发现的氧化蛋白质和DNA似乎首次证明了唾液自由基、抗氧化剂与OSCC之间的直接联系。这对于更好地理解该疾病的发病机制可能很重要，并且可能有助于其诊断和治疗。
