Studies on the carcinogenesis of rhinosinus in relation to reactive oxygen species

活性氧与鼻窦癌发生的关系研究

• 批准号: 12671664
• 负责人: TAKEUCHI Toru
• 金额: $ 2.11万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671664/
• 关键词: Reactive Oxygen Species; Oxidative DNA damage; Cancer in the rhinosinus; Chronic inflammation; Carcinogenesis; Human

We have established a method to determine a typical oxidative DNA damage, 8-hydroxydeoxyguanosine (8OHdG) in the rhinosinus mucosae. That is, extraction of DNA from the mucosae, digestion of DNA to nucleosides with nuclease P1 and alkaline phosphatase, ultra filtration of the nucleosides, HPLC separation of the nucleoside with reversed-phase column, and the detection of 8OHdG with electrochemical detector (ECD). We did the steps from DNA extraction to nucleosides ultra filtration in an anaerobic incubator to reduce the artificial formation of 8OHdG during sample processing.With the method, we determined the levels of 8OHdG in the rhinosinus mucosae from the patients with chronic rhinosinusitis, nasal polyps and papilloma of rhinosinus, and compared the 8OHdG levels with those in normal rhinosinus mucosae. The diagnosis was done microscopically. The samples were obtained from the patients who had been scheduled to remove lesions by operation in Higashiosaka city hospital and had given us the informed consent.The 8OHdG levels were 0.54 in normal mucosae(n=4), 0.59 in nasal polyp(n=7), 0.48 in chronic rhinosinusitis (n=7), and 0.43 in papilloma (n=3). We could not find significant difference between normal and other groups.This is the first study to determine 8OHdG in rhinosinus mucosae. Ultrafiltration was effective to remove contaminants which interfere the 8OHdG analyses by HPLC-ECD, However we could not find significant increase of 8OHdG in chronic rhinosinusitis related samples. Recently the incidence of cancer in the rhinosinus is decreasing. From the present study we considered that the grades of chronic inflammation in rhinosinusitis are not severe enough to induce 8OHdG due to the improvement of the treatments and/or the host status.

我们建立了一种检测鼻窦粘膜中典型的DNA氧化损伤8-羟基脱氧鸟苷（8-OHdG）的方法。即从粘膜中提取DNA，用核酸酶P1和碱性磷酸酶将DNA消化为核苷，超滤核苷，用反相柱进行高效液相色谱分离核苷，用电化学检测器（ECD）检测8 OHdG。为了减少样品处理过程中8 OHdG的人为产生，我们采用厌氧培养箱中从DNA提取到核苷超滤的方法，测定了慢性鼻窦炎、鼻息肉和鼻窦乳头状瘤患者鼻窦粘膜中8 OHdG的含量，并与正常鼻窦粘膜进行了比较。诊断是在显微镜下进行的。样本来自东大坂市立医院预定手术切除病变并同意我们的患者，正常粘膜（n=4）、鼻息肉（n= 7）、慢性鼻窦炎（n =7）和乳头状瘤（n=3）中的8 OHdG水平分别为0.54、0.59、0.48和0.43。本研究首次对鼻窦粘膜中的8-OHdG进行了测定。超滤能有效去除干扰HPLC-ECD分析的杂质，但在慢性鼻窦炎相关样品中未发现8 OHdG的显著增加。最近，鼻窦癌的发病率正在下降。从目前的研究中，我们认为鼻窦炎的慢性炎症程度不足以严重到诱导8 OHdG，这是由于治疗和/或宿主状态的改善。

项目成果

竹内亨: "活性酸素と健康-活性酸素ってなんだろう-がんとの関連から"鹿児島市医報. 40. 8-26 (2001)

竹内彻：“活性氧与健康 - 什么是活性氧？ - 从与癌症的关系”鹿儿岛市医学通报 40. 8-26 (2001)。

Lu, Y., et al.: "Genotoxic effects of a-endosulfan and a-endosulfan on human Hep G2 cells"Environ. Health Perspect.. 108. 559-561 (2000)

Lu, Y., et al.：“α-硫丹和α-硫丹对人 Hep G2 细胞的基因毒性作用”Environ。

Takelchi,T., Kato,N., Watanabe,K. and Morimoto,K.: "Mechanism of oxidative DNA damage inducation in a strict anaerobe, Prevotella melaninogenica"FEMS Microbiol. Lett. 192. 133-138 (2000)

Takelchi，T.，加藤，N.，渡边，K.

Lu,Y., Takeshita,T., Takeuchi,T. and Morimoto,K.: "Genotoxic effects of a-endosulfan and a-endosulfan on human Hep G2 cells"Environ. Health Perspect. 108. 559-561 (2000)

卢Y.，竹下T.，竹内T.

Kanno,Hiroyuki, et al.: "Low Frequency of HLA-A^*0201 allele in patients with Epstein-Barr virus-positive nasal lymphomas with polymorphic reticulosis morphology"International Journal of Cancer. 87. 195-199 (2000)

Kanno、Hiroyuki 等人：“具有多形性网状组织形态的 Epstein-Barr 病毒阳性鼻淋巴瘤患者中 HLA-A^*0201 等位基因的低频率”国际癌症杂志。