Hirano T, Hirano H, Yamaguchi R, Asami S, Tsurudome Y, Kasai H
Department of Environmental Oncology, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
J Radiat Res. 2001 Sep;42(3):247-54. doi: 10.1269/jrr.42.247.
The base excision repair system for 8-hydroxyguanine (8-OH-Gua) is believed to play a role in the prevention of mutations, such as GC-to-TA transversion, which leads to cancer development. However, the exact repair mechanism is still unclear. In this study, we examine whether the repair activity level for 8-hydroxyguanine, one of the major forms of oxidative DNA damage, depends on the sequence of the substrate DNA. We prepared six different oligonucleotides containing 8-hydroxyguanine as substrates and reacted them with crude extracts from the livers and kidneys of 8-week-old Sprague-Dawley rats. As a result, up to a 10-fold difference in the repair activity levels was observed, depending on the substrates used. Based on this observation, we suggest that the repair systems may act with sequence specificity on the damaged DNA.
8-羟基鸟嘌呤(8-OH-Gua)的碱基切除修复系统被认为在预防诸如GC到TA颠换等导致癌症发生的突变中发挥作用。然而,确切的修复机制仍不清楚。在本研究中,我们研究了氧化DNA损伤的主要形式之一8-羟基鸟嘌呤的修复活性水平是否取决于底物DNA的序列。我们制备了六种不同的含8-羟基鸟嘌呤的寡核苷酸作为底物,并将它们与8周龄Sprague-Dawley大鼠肝脏和肾脏的粗提物反应。结果发现,根据所使用的底物不同,修复活性水平存在高达10倍的差异。基于这一观察结果,我们认为修复系统可能对受损DNA具有序列特异性作用。