Role of Helicobacter pylori CagA+ infection in determining oxidative DNA damage in gastric mucosa
Role of Helicobacter pylori CagA+ infection in determining oxidative DNA damage in gastric mucosa
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DOI：
10.1080/003655202317316033
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发表时间：
2002-04-01
影响因子：
1.9
通讯作者：
Gasbarrini, A
中科院分区：
文献类型：
--
作者：
Papa, A;Danese, S;Gasbarrini, A
背景资料：虽然幽门螺杆菌是胃癌的一个危险因素，但细菌在这种恶性肿瘤发展中的作用并没有精确定义。活性氧（Reactive oxygen species，ROS）通过诱导DNA损伤在肿瘤发生中起重要作用。本研究的目的是：1）根据H. pylori状态和细胞毒性相关基因产物A（CagA）2），以确定ROS产生和8-OHdG量之间的关系。方法：胃活检标本来自60例连续患者。通过鲁米诺增强的化学发光来测量ROS产生。8-OHdG检测采用免疫过氧化物酶法，使用特异性抗8-OHdG单克隆抗体。结果：60例患者中40例（67%）为H。幽门阳性在H阳性患者中，ROS的产生显著更高。pylori感染与阴性相比。8-在30例患者中进行了OHdG检测，其中还研究了CagA的存在。8-OHdG在14/20例（70%）H中呈高表达。pylori阳性者13例（+），1例（-）;幽门阴性患者。ROS产生与8-OHdG含量呈显著相关。结论：H. CagA（+）菌株的幽门螺杆菌感染与ROS的最高产生相关，ROS的最高产生对应于严重的氧化性DNA损伤。这一系列事件支持了H. pylori细胞毒菌株可能是慢性胃炎向胃癌发展的驱动力。
Background: Although Helicobacter pylori is a risk factor for gastric cancer, the role of the bacterium in the development of this malignancy is not defined precisely. Reactive oxygen species (ROS) could play an important role in carcinogenesis by inducing DNA damage. The aims of the present study were: 1) to assess the production of ROS and 8-hydroxy-2'-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA injury, in gastric mucosa, according to H. pylori status and cytotoxic associated gene product A (CagA) 2) to determine the relationship between ROS generation and amount of 8-OHdG. Methods: Gastric biopsy specimens were obtained from 60 consecutive patients. ROS generation was measured by luminol enhanced chemiluminescence. 8-OHdG detection was performed by an immunoperoxidase method, using a specific anti 8-OHdG monoclonal antibody. Results: 40/60 patients (67%) were H. pylori-positive. ROS generation was significantly higher in patients positive for H. pylori infection as compared to negative. 8-OHdG detection was performed in 30 patients in which CagA presence was also investigated. High expression of 8-OHdG was detected in 14/20 (70%) H. pylori-positive patients (13 CagA(+) and 1 CagA(-)) and in 2/10 (20%) H. pylori-negative patients. A significant correlation was found between ROS production and 8-OHdG content. Conclusion: H. pylori infection by a CagA(+) strain is associated with the highest production of ROS to which a severe oxidative DNA damage corresponds. This sequence of events could support the hypothesis that the oxygen-free radicals-mediated damage due to H. pylori cytotoxic strains could be a driving force that leads from chronic gastritis to gastric carcinoma.