OXIDATIVE DNA DAMAGE AND HEPATITIS B VIRUS ONCOGENESIS

这项提议的目的是检验氧化DNA 损伤在肝细胞癌发生发展中的作用 人类继发于乙肝病毒(乙肝、肝细胞癌)。 我们推测，乙肝肝细胞癌将含有更多的DNA加合物。 8-羟基-2‘-脱氧鸟苷(8-OH-DG)是这种类型的标记物。 损坏。为了验证这一假设，将对以下几个方面进行研究 接受肝大部切除治疗乙肝肝细胞癌患者：医学 病史；乙肝病毒和丙型肝炎的血清病毒标志物；血清甲型 肝细胞癌相对不敏感的标志物--Feto蛋白；分析8- 肝(肿瘤及癌旁组织)中的OH-DG。“肿瘤控制”小组 (乙肝病毒阴性的肝细胞癌和肝外肿瘤转移到 肝脏部分切除)将在类似的研究中 时尚将是终末期酒精性肝病的“疾病控制” 疾病(ALD)接受肝移植(LT)。10-15名病人 每组每年都将进行研究，与以前一致 在我们机构诊断乙肝肝细胞癌的经验。 我们还建议尿8-OH-dG将是一个有用的标志物肝脏8-羟基-DG。 哦-DG。因此，上述患者的肝脏8-OH-dg值将是 与两份尿样中8-OH-DG的相关性 术前尿液和术中尿液。尿样 来自年龄和性别与乙肝病毒相匹配的健康志愿者 肝细胞癌患者，也将进行8-OH-DG分析。先导研究 健康对照组将检查个体内变异和 禁食对尿8-OH-DG的影响由于肝移植的无肝期 程序提供了一个独特的机会来调查 肝8-OH-dG与尿8-OH-dG的比值，后者将在LT期间测定： 在无肝期之前、期间和之后。 精心挑选的临床小组和最先进的组合 8-羟基-DG技术代表了一种测试新技术的极好手段 乙肝病毒致癌假说有望改进 筛查、治疗，并最终预防乙肝肝细胞癌。

The purpose of this proposal is to test the hypothesis that OXIDATIVE DNA DAMAGE PLAYS A ROLE IN THE DEVELOPMENT OF HEPATOCELLULAR CARCINOMA SECONDARY TO HEPATITIS B VIRUS (HBV HCC) IN MAN. We postulate that HBV HCC will contain increased amounts of the DNA adduct 8-hydroxy-2'-deoxyguanosine (8-OH-dG), which is a marker of this type of damage. To test this hypothesis, the following studies will be done on patients undergoing martial hepatic resection for HBV HCC: medical history; serum viral markers for HBV and for Hepatitis C; serum alpha feto-protein, a relatively insensitive marker of HCC; and analysis of 8- OH-dG in liver (tumor and peri-tumoral tissue). "Tumor control" groups (patients with HBV negative HCC and with extrahepatic tumor metastatic to liver undergoing partial hepatic resection) will be studied in similar fashion as will "disease control" patients with endstage alcoholic liver disease (ALD) undergoing liver transplantation (LT). Ten-fifteen patients per group per year will be studied, consistent with the previous experience at our institution with the diagnosis of HBV HCC. We also propose that urinary 8-OH-dG will be a useful marker of hepatic 8- OH-dG. Thus hepatic 8-OH-dG values from the above patients will be correlated with urinary 8-OH-dG in two urine samples obtained in the preoperative period and in urine obtained intraoperatively. Urine samples obtained from healthy volunteers who are age- and sex-matched to the HBV HCC patients, will also be analyzed for 8-OH-dG. Pilot studies in the healthy control group will examine intra-individual variation and the effect of fasting on urinary 8-OH-dG. Since the anhepatic phase of the LT procedure offers a unique opportunity to investigate the contribution of hepatic 8-OH-dG to urinary 8-OH-dG, the latter will be measured during LT: before, during, and following the anhepatic phase. The combination of carefully selected clinical groups and state-of the art technology for 8-OH-dG represent an excellent means of testing new hypothesis of HBV carcinogenesis which could lead the way to improve screening, therapy, and ultimately, prevention of HBV HCC.