Kadioglu Ela, Sardas Semra, Ergun Meltem, Unal Selahattin, Karakaya Ali Esat
Toxicology Department, Faculty of Pharmacy, Gazi University, Ankara, Turkey.
Toxicol Ind Health. 2010 Mar;26(2):67-79. doi: 10.1177/0748233709359278. Epub 2010 Jan 7.
Determination of the genetic alterations, which play a role in the etiology of Barrett's esophagus (BE), could help identify high-risk individuals for esophageal adenocarcinoma (EA). The aim of the present study was to investigate the role of oxidative DNA damage, glutathione (GSH) concentration as oxidative stress parameters and DNA repair capacity, GSTM1, SOD1 Ala16Val and OGG1 Ser326Cys genetic polymorphisms as individual susceptibility parameters in the etiology of BE. The study groups comprised BE patients who were clinically diagnosed (n = 40) and a healthy control group (n = 40). Basal DNA damage, pyrimidine and purine base damage after H(2)O(2) induction, H( 2)O(2) sensitivity, DNA repair capacity, oxidized pyrimidine and purine base damage repair were evaluated in peripheral blood lymphocytes with a modified comet assay using specific endonucleases (Endo III and Fpg). Polymerase chain reaction-restriction length polymorphism (PCR-RFLP)-based assays were used for genotyping. The patient group showed elevated levels of basal DNA damage, pyrimidine base damage and H(2)O(2) sensitivity as compared to controls (p < .05). DNA repair capacity, oxidized pyrimidine and purine base damage repair capacity, were not statistically different between patients and controls. GSH concentration was found to be significantly lower in smoking patients than in the controls (p < .05). None of the genetic variations changed the risk of having BE disease. However, patients carrying the variant OGG1 Cys allele showed elevated levels of pyrimidine base damage as compared to patients carrying the wild-type OGG1 Ser (p < .05). The results of this study point to a role of oxidative DNA damage in BE. However, DNA repair capacity, GSTM1, SOD1 Ala16Val and OGG1 Ser326Cys genetic polymorphisms appeared to play no role in the individual susceptibility to this disease.
确定在巴雷特食管（BE）病因中起作用的基因改变，有助于识别食管腺癌（EA）的高危个体。本研究的目的是探讨氧化DNA损伤、谷胱甘肽（GSH）浓度作为氧化应激参数以及DNA修复能力、GSTM1、SOD1 Ala16Val和OGG1 Ser326Cys基因多态性作为个体易感性参数在BE病因中的作用。研究组包括临床诊断的BE患者（n = 40）和健康对照组（n = 40）。使用特定核酸内切酶（Endo III和Fpg）的改良彗星试验评估外周血淋巴细胞中的基础DNA损伤、H(2)O(2)诱导后的嘧啶和嘌呤碱基损伤、H(2)O(2)敏感性、DNA修复能力、氧化嘧啶和嘌呤碱基损伤修复。基于聚合酶链反应-限制性片段长度多态性（PCR-RFLP）的分析用于基因分型。与对照组相比，患者组的基础DNA损伤、嘧啶碱基损伤和H(2)O(2)敏感性水平升高（p <.05）。患者和对照组之间的DNA修复能力、氧化嘧啶和嘌呤碱基损伤修复能力无统计学差异。发现吸烟患者的GSH浓度显著低于对照组（p <.05）。没有一种基因变异改变患BE疾病的风险。然而，与携带野生型OGG1 Ser的患者相比，携带变异OGG1 Cys等位基因的患者嘧啶碱基损伤水平升高（p <.05）。本研究结果表明氧化DNA损伤在BE中起作用。然而，DNA修复能力、GSTM1、SOD1 Ala16Val和OGG1 Ser326Cys基因多态性似乎在个体对该疾病的易感性中不起作用。
