HUMAN LIVER CARCINOGENESIS

乙型和丙型肝炎病毒作为肝细胞因子的协同作用 癌症(HCC)。 我们继续在高肝癌患者中进行分子流行病学研究 中国启东风险地理区。和我们的长期同事 孙宗棠，关于乙肝病毒和丙型肝炎病毒相加效应的假说 在肝细胞癌的发生过程中正在进行测试。我们最近做了 分析了112例组织学病例对照研究的数据 确诊的肝细胞癌病例和225例年龄和性别匹配的对照。这个 结果与我们的假设一致。值得注意的是， 启东地区居民经年龄调整后的肝癌年死亡率 慢性乙肝和丙型肝炎病毒携带者估计占7%。 乙肝病毒和DNA修复。 我们和其他人之前已经报道过P53可以调节核苷酸 切除修复。使用宿主重新激活试验，我们的初步数据 表明HBx抑制重新激活，即修复 紫外光(UV-C，254 nm)对质粒有损伤作用。这导致了 HBx抑制P53与XPB或XPD DNA解旋酶结合的假说 在碱基转录-核苷酸切除修复复合体TFIIH中。 我们先前已经证明HBx蛋白在体外抑制P53 绑定到XPB。然而，HBX没有绑定到XPB，HBX确实绑定到了 P53的羧基末端，也是XPB结合的部位。我们是 目前正在研究HBX与其他成员绑定的假设 TFIIH多蛋白复合体。

Hepatitis B and C Viruses Cooperate as Factors of Hepatocellular Carcinoma (HCC). We continue to conduct molecular epidemiology studies in the high HCC risk geographic area in Qidong, China. With our longstanding coworker Zong-tang Sun, the hypothesis that HBV and HCV have additive effects in hepatocellular carcinogenesis is being tested. We have recently analyzed data from our case-control study involving 112 histologically proven HCC cases, and 225 age- and gender-matched controls. The results are consistent with our hypothesis. Remarkably, the age-adjusted annual HCC mortality rate for Qidong residents with chronic HBV and HCV carriers is estimated to be 7%. Hepatitis B Virus and DNA Repair. We and others have previously reported that p53 can modulate nucleotide excision repair. Using a host reactivation assay, our preliminary data indicate that HBx inhibits reactivation, i.e., repair of the ultraviolet light (UV-C, 254 nm) damage plasmid. This leads to the hypothesis that HBx inhibits p53 binding to XPB or XPD DNA helicases in the basal transcription-nucleotide excision repair complex, TFIIH. We have previously demonstrated that HBx protein inhibits in vitro p53 binding to XPB. Whereas, HBx did not bind to XPB, HBx does bind to the carboxyl terminus of p53 which also is the site of XPB binding. We are currently investigating the hypothesis that HBx binds to other members of the TFIIH multiprotein complex.