8-Hydroxyguanine, a DNA adduct formed by oxygen radicals: its implication on oxygen radical-involved mutagenesis/carcinogenesis.

8-Hydroxyguanine, a DNA adduct formed by oxygen radicals: its implication on oxygen radical-involved mutagenesis/carcinogenesis.
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DOI:
10.2131/jts.16.supplementi_95
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发表时间:
1991-02
期刊:
The Journal of toxicological sciences
影响因子:
--
通讯作者:
H. Kasai;M. Chung;D. S. Jones;H. Inoue;H. Ishikawa;H. Kamiya;E. Ohtsuka;S. Nishimura
H. Kasai;M. Chung;D. S. Jones;H. Inoue;H. Ishikawa;H. Kamiya;E. Ohtsuka;S. Nishimura
中科院分区:
其他
文献类型:
--
作者:
H. Kasai;M. Chung;D. S. Jones;H. Inoue;H. Ishikawa;H. Kamiya;E. Ohtsuka;S. Nishimura

文献摘要

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氧自由基已被认为参与突变/致癌作用。DNA中鸟嘌呤残基的C-8位在体外被各种氧自由基产生剂羟基化以产生DNA中的8-羟基鸟嘌呤(8-OH-Gua)。8-OH-Gua的形成也被观察到在体内细胞DNA中通过辐射或氧自由基形成致癌物。DNA中的8-OH-Gua残基经常在8-OH-Gua残基本身的位置上被误读,而且在8-OH-Gua旁边的相邻残基上也被误读。当8-OH-Gua特异性地取代第12位密码子中的第二鸟嘌呤并转移到NIH 3 T3中时,受体细胞转化为恶性细胞类型。E.发现大肠杆菌中含有一种能特异性识别8-OH-Gua残基的核酸内切酶,它能切割修饰碱基前后的DNA链。所获得的数据意味着,8-OH-Gua形成的DNA在体内被认为是一个异常的修饰的碱基,如果不修复,发挥作用,在介导的氧自由基参与的突变/致癌作用。
Oxygen radicals have been suggested to be involved in mutation/carcinogenesis. The C-8 position of guanine residues in DNA is hydroxylated to produce 8-hydroxyguanine (8-OH-Gua) in DNA in vitro by various oxygen radical producing agents. The formation of 8-OH-Gua was also observed in cellular DNA in vivo by radiation or oxygen radical forming carcinogens. The 8-OH-Gua residue in DNA is often misread in the position of 8-OH-Gua residue itself but also at neighboring residues next to 8-OH-Gua. When second guanine in codon 12 was specifically replaced with 8-OH-Gua and transferred to NIH3T3, the recipient cells were transformed to malignant cell type. E. coli was found to contain an endonuclease which specifically recognizes 8-OH-Gua residue and cleave DNA strand before and after the modified base. The data obtained imply that 8-OH-Gua formed in DNA in vivo is recognized as an abnormal modified base which, if not repaired, play a role in the mediation of oxygen radical-involved mutation/carcinogenesis.