原发性肝癌DNA修复酶hOGG1,hMTH1基因表达与DNA氧化损伤的修复

Expression of DNA repair genes hMTH1 and hOGG1 and repair of oxidative dam- age of DNA in hepatocellular carcinoma

目的:探讨DNA修复酶hOGG1和hMTH1基因表达对DNA氧化损伤产物8-OHdG的修复调控及其在肝癌发生和防御机制中的作用.方法:RT/实时PCR定量检测23例HCC患者癌和癌旁组织中hOGG1和hMTH1基因的表达,HPLC/ECD法测定其8-OHdG含量.结果:HCC患者癌旁组织8-OHdG含量明显高于癌组织(133vs56nmol/gDNA,P<0.01),且与炎症程度密切相关.而癌组织中hMTH1表达较癌旁组织显著升高(0.476vs0.256,P<0.05).hOGG1表达在HCC和癌旁组织间无显著差异.但hOGG1和hMTH1表达之间存在显著的相关性(r=0.81,P<0.01).结论:慢性肝脏炎症反应可能是肝细胞内DNA氧化损伤及肝细胞癌变的重要原因.DNA修复酶hOGG1和hMTH1可能协同参与肝细胞内DNA氧化损伤的修复,在肝癌发生和防御机制中起到作用.

AIM:To study the regulatory effect of expression of hMTH1 and hOGG1 genes on the oxidative DNA-adduct 8-OHdG levels in hepatocellular carcinoma (HCC) and non-tumourous liver tissue in order to elucidate the role of the DNA repair enzymes in hepatocarcinogenesis. METHODS:A reverse transcription (RT)/real-time-poly- merase chain reaction (PCR) assay was used to semi-quan- tify mRNA of hMTH1 and hOGG1 in HCC and non-tumourous liver tissue from 23 patients with HCC. 8-OHdG levels were determined by HPLC/ECD. RESULTS:The median of 8-OHdG levels in non-tumourous liver tissue was significantly (133 vs 56 nmol/g DNA, P <0.01) higher than that in HCC tissue. This was correlated with the severity of inflammation in non-tumourous liver tissues. The expression of hMTH1 was significantly (0.476 vs 0.256,P <0.05) higher in HCC tissue than that in non-tumourous liver tissue. No difference of expression of hOGG1 between non-tumourous liver and HCC tissue was seen.A significant correlation was detected between the expression of hMTH1 and hOGG1 (r = 0.81, P <0.01). CONCLUSION:Elevated 8-OHdG levels in non-tumourous liver are likely due to the increased generation of reactive oxygen intermediates by infiltrating inflammatory cells. The expression of DNA repair enzymes hOGG1 and hMTH1 may involve cooperatively in the repair oxidative DNA adduct 8-OHdG and have a potential role in hepatocarcinogenesis.