微囊藻毒素-LR(MC-LR)能引发肝细胞毒性效应,HBV可通过多种信号通路诱导肝细胞癌变，迄今对两者能否产生协同作用知之甚少。本项目的预实验发现广西肝癌高发区水源存在MC-LR，当地人群HBV感染率高且某些HBV基因变异与肝癌发病相关，但两者相互作用的机制有待进一步探讨。为此本项目提出：MC-LR与HBV变异可联合导致DNA氧化损伤效应和抑制PP2A活性、调控下游MAPK家族蛋白表达而引起肝细胞癌变。为验证这一假说，本项目拟采用流行病与细胞分子生物学结合的研究设计，首先在广西肝癌高发区开展MC-LR暴露及HBV感染、变异与肝癌关系的生态流行病学研究，再采用病毒转染、MTT、FCM、DNA损伤检测、抗氧化剂干预、Western blot等手段，在细胞分子水平从氧化应激效应和磷酸化的角度探讨MC-LR与HBV变异联合作用的细胞效应及调控机制。预期结果可为肝癌的综合防治提供科学数据及理论参考。

Microcystin-LR can cause liver cell toxicity effect, HBV can lead to hepatocellular carcinoma by mediating various signaling pathway. But it is still poorly understood for the synergy of both. This project found microcystin-LR in water source of high incidence area of liver cancer in Guangxi through preliminary experimental, the HBV infection rate was high in local people and some HBV variations connected with hepatocellular carcinoma, but the interaction mechanism of them remains to be further discussed.So this project hypothesized that MC - LR associated with HBV mutants can lead to DNA oxidative damage effect and inhibition of PP2A activity to regulate the expression of downstream MAPK family protein and result to hepatocellular carcinogenesis. To test this hypothesis, this study will combine the epidemiology with cell molecular biology, to firstly investigate the relationship between microcystin-LR exposure and HBV infection, variation with hepatocellular carcinoma in the high incidence area of liver cancer in Guangxi by ecology study, then explore the cell effect and regulatory mechanism of MC - LR joint with HBV by virus transinfection, MTT, FCM, genetic toxicity test, antioxidant intervention, Western blot and so on from the perspective of the oxidative stress and phosphorylation in cell and molecular level. It is expected to provide scientific data and theory reference for the comprehensive prevention and treatment of hepatocellular carcinoma.