Mutagenicity of secondary oxidation products of 8-oxo-7,8-dihydro-2′-deoxyguanosine 5′-triphosphate (8-hydroxy-2′- deoxyguanosine 5′-triphosphate)
Mutagenicity of secondary oxidation products of 8-oxo-7,8-dihydro-2′-deoxyguanosine 5′-triphosphate (8-hydroxy-2′- deoxyguanosine 5′-triphosphate)
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DOI：
10.1016/j.mrfmmm.2011.05.015
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发表时间：
2011-09-01
影响因子：
2.3
通讯作者：
Kamiya, Hiroyuki
中科院分区：
文献类型：
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作者：
Hori, Mika;Suzuki, Tetsuya;Kamiya, Hiroyuki
8-氧代-7，8-二氢鸟嘌呤（8-hydroxyguanine，8-hydroxyguanine）比正常的核碱基更容易被氧化，可产生螺亚氨基二乙内酰脲（spiroiminodihydetuin，Sp）和胍基乙内酰脲（guanidinohydetuin，Gh）。这些8-氧代-7，8-二氢鸟嘌呤的次级氧化产物在DNA内形成时具有高度致突变性。为了评价核苷酸池中8-氧代-7，8-二氢-2 '-脱氧鸟苷5'-三磷酸（8-羟基-2 '-脱氧鸟苷5'-三磷酸）相应氧化产物的致突变性，用H2 O2处理mutT基因缺陷的大肠杆菌细胞，并分析诱导的突变。此外，还将Sp和Gh的2 ′-脱氧核苷5 ′-三磷酸衍生物导入感受态E. coli细胞。H_2O_2处理mutT E. coli细胞中G：C -> T：A和A：T -> T：A突变增加。然而，掺入外源性Sp和Gh 2 '-脱氧核糖核苷酸并没有显著增加突变频率。这些结果表明，8-氧代-7，8-二氢-2 '-脱氧鸟苷5'-三磷酸的氧化产物可诱导G：C -> T：A和A：T -> T：A突变，Sp和Gh的2 '-脱氧核苷5'-三磷酸衍生物与DNA中的碱基相比，具有很弱的致突变性。(C)2011 Elsevier BM. All rights reserved.
8-Oxo-7,8-dihydroguanine (8-hydroxyguanine) is oxidized more easily than normal nucleobases, which can produce spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh). These secondary oxidation products of 8-oxo-7,8-dihydroguanine are highly mutagenic when formed within DNA. To evaluate the mutagenicity of the corresponding oxidation products of 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-hydroxy-2'- deoxyguanosine 5'-triphosphate) in the nucleotide pool, Escherichia coli cells deficient in the mutT gene were treated with H2O2, and the induced mutations were analyzed. Moreover, the 2'-deoxyriboside 5'-triphosphate derivatives of Sp and Gh were also introduced into competent E. coli cells. The H2O2 treatment of mutT E. coli cells resulted in increase of G:C -> T:A and A:T -> T:A mutations. However, the incorporation of exogenous Sp and Gh 2'-deoxyribonucleotides did not significantly increase the mutation frequency. These results suggested that the oxidation product(s) of 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate induces G:C -> T:A and A:T -> T:A mutations, and that the 2'-deoxyriboside 5'-triphosphate derivatives of Sp and Gh exhibit quite weak mutagenicity, in contrast to the bases in DNA. (C) 2011 Elsevier BM. All rights reserved.