Matsubara K, Tokino T
Institute for Molecular and Cellular Biology, Osaka University, Suita, Japan.
Mol Biol Med. 1990 Jun;7(3):243-60.
Hepatitis B virus (HBV) DNA integrates into human hepatocyte DNA. We have gathered the available data on the structure of the integrants from human hepatocellular carcinomas, and classified them into those that seem to represent primary integrants and those that are the products of secondary rearrangements. By means of structural analyses of the possible primary integrants, we deduced that the replication intermediates of the viral genome are the preferred substrates for integration. The integrated HBV DNA and the target cellular DNA are invariably associated with deletions, possibly reflecting the substrate for, and the mechanism of, the integration reaction. The target cell DNA sequence, as well as the target site of integration in chromosomes, seems to be selected randomly, suggesting that HBV DNA integration should bring about random mutagenic effects. Several samples recovered from hepatocellular carcinomas show that the integrated HBV DNA can mediate secondary rearrangements of chromosomes, such as translocations, inversions, deletions and (possibly) amplifications. Thus, HBV DNA integration causes multiple mutagenic effects. We argue that during hepatitis infection, the tendency of rearrangement of hepatocyte chromosomes is combined with the forcible turnover of cells. This is a constantly operating system for the selection of cells that grow better than average cells, possibly involving important steps in multistaged hepatocarcinogeneses.
乙型肝炎病毒（HBV）DNA整合到人类肝细胞DNA中。我们收集了来自人类肝细胞癌的整合体结构的现有数据，并将它们分为似乎代表初级整合体的那些和那些是二级重排产物的那些。通过对可能的初级整合体的结构分析，我们推断病毒基因组的复制中间体是整合的首选底物。整合的HBV DNA和靶细胞DNA总是与缺失相关，这可能反映了整合反应的底物和机制。靶细胞DNA序列以及染色体中的整合靶位点似乎是随机选择的，这表明HBV DNA整合应该产生随机诱变效应。从肝细胞癌中回收的几个样本表明，整合的HBV DNA可以介导染色体的二级重排，如易位、倒位、缺失和（可能的）扩增。因此，HBV DNA整合会导致多种诱变效应。我们认为，在肝炎感染期间，肝细胞染色体重排的趋势与细胞的强制更新相结合。这是一个不断运行的系统，用于选择比普通细胞生长更好的细胞，可能涉及多阶段肝癌发生中的重要步骤。
