8-羟基脱氧鸟苷(8-OHdG)是鸟嘌呤被反应性活性氧类（ROS）氧化损伤的主要产物，具有极强的致DNA突变能力。在生理情况下，8-OHdG可被hMTH1有效水解，错误掺入DNA的8-OHdG也可被hOGG1/hMYH切除修复。我们先前的研究发现乙型肝炎病毒X蛋白（HBx）导致肝细胞ROS增加并使8-OHdG 增多，并且HBx抑制hMTH1、hOGG1及hMYH基因转录。本研究从8-OHdG导致基因组DNA突变角度出发，探讨HBx在肝癌发生发展中的作用。主要研究内容包括：1. HBx抑制hMTH1基因转录的机制以及HBx是否通过降低hMTH1干扰8-OHdG的清除；2. HBx抑制hOGG1及hMYH基因转录的机制以及是否通过降低hOGG1/hMYH干扰DNA突变修复，导致8-OHdG 引起的肝细胞DNA突变率增加。本研究所获得的结果将有助于更深入了解HBV致肝癌机制。

8-hydroxy-2'-deoxyguanosine (8-OHdG) with a strong ability to cause DNA mutations, is a predominant from of reactive oxygen species (ROS)-induced oxidative lesion. Under physiological conditions, 8-OHdG could be hydrolyzed by hMTH1, while misincorporated 8-OHdG in DNA could be excised and repaired by hOGG1/hMYH. In our previous studies, we found that hepatitis B virus X protein (HBx) could increase intracellular ROS and 8-OHdG level, and inhibit the transcription of hMTH1, hOGG1and hMYH. In this study, we aim to elucidate the role of HBx in hepatocarcinogenesis from the perspective of 8-OHdG-mediated DNA mutation, the main contents include:1.Mechanisms involved in the inhibitory effects of HBx on hMTH1 gene transcription, and whether HBx interference with 8-OHdG clearance through reducing the expression of hMTH1; 2.Mechanisms involved in the inhibitory effects of HBx on hOGG1/hMYH gene transcription, and whether HBx interfere with the mutation repairing through reducing the expression of hOGG1/hMYH, which leading to the increasing of 8-OHdG-induced DNA mutation in hepatocytes. The results obtained in this study will contribute to a better understanding of the HBV-related hepatocarcinogenesis.