乙肝病毒对DNA修复基因和肝癌发生的作用

The effect of hepatitis B virus on DNA repair gene expression and hepatocarcinogenesis

目的 以HBV转基因动物模型研究乙型肝炎病毒 (HBV) ,黄曲霉毒素 (AFB1) ,DNA修复基因和肝细胞肝癌 (HCC)发生的关系。方法 对HBVx基因转基因小鼠以相同的方式和剂量给予黄曲霉毒素 (AFB1)攻击 ,比较肝癌的发生率 ;同时用逆转录———热标记扩增 (RT -HOT -PCR)的方法 ,检查HBVx基因转基因小鼠HBVx整合阳性和阴性以及AFB1攻击后 ,癌组织与癌旁组织的DNA修复基因Brca2和Nthl1的RNA表达水平。结果 (1)黄曲霉毒素诱导 ,5 2周肝癌发生率HBVx整合阳性小鼠 2 9只 ,14只发生肝癌 (48.3% ) ;HBVx整合阴性小鼠 15只 ,3只发生肝癌 (2 0 .0 % )。两者有显著的差异 (P <0 .0 1)。(2 )HBVx整合阳性小鼠的肝组织DNA修复基因Brca2和Nthl1的RNA表达水平都低于HBVx整合阴性小鼠。经AFB1攻击形成的肝癌和癌旁组织 ,其DNA修复基因Brca2和Nthl1的RNA表达水平也低于HBVx整合阴性小鼠。结论 结果表明HBVx在宿主细胞的整合 ,影响了宿主DNA修复能力 ,从而导致宿主对致癌物质的敏感性增加 ,最终引起肝癌发生率的增加。

Objective To investigate the hepatitis B virus(HBV),AFB1,DNA repair and the incidence of Hepatocellular carcinoma(HCC) in the HBVx transgenic mice. Methods HBVx positive and HBVx negative transgenic mice were treated with and without AFB1 and then the HCC incidence was observed. DNA repair genes Brca2, Nthl1 expressions were measured by RT-HOT-PCR. Result (1) Fourteen of 29 (48.3%) mice developed HCC in group of HBVx positive and AFB1 treatment. While only 3 of 15 mice ( 20.0%) developed HCC in group of HBVx negative and AFB1 treatment. P <0.01. (2) The expressions of both Brca2 and Nthl1 were lower in groups of HBVx positive than HBVx negative group. AFB1 treatment groups are lower than HBVx negative group. Conclusion These result implicate that the infection of HBV enhanced incidence of HCC by altering DNA repair system.