氧化/还原因子ref-1在肺癌组织中的细胞定位表达及与8-OH-dG的关系

目的氧化/还原因子-1(ref-1),也称为AP核酸内切酶(APE),是氧化还原和DNA碱基切除修复途径中的重要一员.本研究旨在探讨ref-1在肺癌中的表达及其与氧化损伤标志8-羟基-脱氧鸟苷(8-OH-dG)的关系. 方法用免疫组化法检测150例肺癌组织、120例癌旁肺组织、40例肺良性病变和40例正常肺组织中氧化/还原因子ref-1基因的蛋白质表达;分析有关暴露因素对ref-1表达的影响,探讨ref-1基因与8-OH-dG的关系. 结果肺癌和正常肺组织皆有ref-1的表达,但ref-1在细胞内的定位有所不同,70.0%(105/150)的肺癌组织ref-1从通常的胞核定位移位到胞浆,仅7.5%(3/40)的正常肺组织有ref-1移位胞浆的现象,两者差异显著,P<0.01.未发现肺癌患者的性别、年龄、吸烟和肿瘤家族史等因素与ref-1细胞定位之间有联系.ref-1移位胞浆与肺组织中8-OH-dG的含量呈显著正相关,Spearman相关系数为0.702,P<0.01. 结论 ref-1的细胞定位对其氧化/还原和修复功能有着重要影响,可作为监测细胞DNA修复功能的指标.

The expression of redox factor 1 (ref-1) in situ and its relationships to 8-OH-dG in lung cancer and normal tissues separately

Objective Redox factor 1 (ref-1), also known as AP endonuclease (APE), is one of the very important components of DNA base excision repair and redox. We investigated the expression of ref-1 in situ and its relationships to 8-Hydroxyguanine(8-OH-dG)in lung cancer and normal tissues, respectively. Methods The protein expressions of ref-1 in 150 cases of human lung cancer tissues, 120 adjacent lung tissues without cancer cells, 40 benign lung lesions, 40 normal lung tissues were measured by immunohistochemistry. The effects of some exposure factors on the expression of ref-1 gene were analyzed. The relationship between ref-1 and 8-OH-dG adduct was investigated. Results Protein expression of ref-1 was observed in all lung cancer tissues and normal lung tissues, but it varied with the cellular locations. The ref-1 expression customarily located in nucleus. In 105 of 150 (70.0%) lung cancer tissues and 3 of 40 (7.5%) normal lungs, the shifts of ref-1 were both observed from nucleus to cytoplasm, but the difference was highly significant, P<0.01.The cellular location of ref-1 was not correlated with sex, age, smoking status and family tumor history. The level of 8-OH-dG was significantly correlated with ref-1 cytoplasm location. Spearman r coefficient was 0.702, P<0.01. Conclusion The cellular location of ref-1 may affect this gene's function of redox and DNA repair. And the cellular location of ref-1 could be used as a surveillance biomarker of DNA repair capacity.