Dvorak K, Fass R, Dekel R, Payne C M, Chavarria M, Dvorakova B, Bernstein H, Bernstein C, Garewal H
Department of Cell Biology and Anatomy, The University of Arizona, Tucson, AZ 85724, USA.
Dis Esophagus. 2006;19(5):366-72. doi: 10.1111/j.1442-2050.2006.00596.x.
Barrett's esophagus (BE) patients demonstrate a higher distal esophageal acid exposure profile than other gastroesophageal reflux disease patients. Cellular oxidative stress has been proposed to contribute to the development of BE and esophageal adenocarcinoma. However, a relationship between low esophageal pH and oxidative stress has yet to be elucidated. The aim of this study was to determine the duration of low pH exposure in the esophagus of BE patients compared to those with erosive esophagitis (EE) and to test if brief exposure to low pH leads to the induction of reactive oxygen species (ROS). Seventy-three patients with BE or EE were evaluated by 24-hour esophageal pH monitoring and the percentage of time during which there was exposure to pH < or = 4 and pH < or = 2 was recorded. In vitro, Seg-1 and Het-1A cells were evaluated after brief exposure to pH4 or pH2 by flow cytometry and fluorescent microscopy for the production of ROS. BE patients demonstrated a significantly higher exposure to low pH values (pH < or = 2) than EE patients. The mean percent total time, duration and mean number of reflux episodes at pH < or = 2 were 2.8 +/- 0.53%, 28.8 +/- 3.6 seconds and 79 +/- 11.4 episodes in BE patients, whereas in EE patients they were significantly less, 1.16 +/- 0.3%, 15.6 +/- 1.2 seconds and 48.3 +/- 8.8 episodes, respectively (P < 0.05). In vitro experiments indicate that esophageal cells, when exposed to pH 2, produce ROS. In vitro studies using brief pH 2 exposure are biologically relevant to the clinical situation. Our studies indicate that such exposure induces oxidative stress. This stress may cause DNA damage, mutations and progression to cancer.
巴雷特食管(BE)患者的食管远端酸暴露情况比其他胃食管反流病患者更为严重。细胞氧化应激被认为与BE和食管腺癌的发生有关。然而,食管低pH值与氧化应激之间的关系尚未阐明。本研究的目的是确定BE患者与糜烂性食管炎(EE)患者食管低pH暴露的持续时间,并测试短暂暴露于低pH值是否会导致活性氧(ROS)的产生。通过24小时食管pH监测对73例BE或EE患者进行评估,并记录pH≤4和pH≤2时的暴露时间百分比。在体外,将Seg-1和Het-1A细胞短暂暴露于pH4或pH2后,通过流式细胞术和荧光显微镜评估ROS的产生。BE患者的低pH值(pH≤2)暴露明显高于EE患者。BE患者在pH≤2时的总时间平均百分比、持续时间和反流发作平均次数分别为2.8±0.53%、28.8±3.6秒和79±11.4次,而EE患者则明显较少,分别为1.16±0.3%、15.6±1.2秒和48.3±8.8次(P<0.05)。体外实验表明,食管细胞暴露于pH2时会产生活性氧。使用短暂pH2暴露的体外研究与临床情况具有生物学相关性。我们的研究表明,这种暴露会诱导氧化应激。这种应激可能导致DNA损伤、突变和癌症进展。