Mutagenicities of 8-Hydroxyguanine and 2-Hydroxyadenine Produced by Reactive Oxygen Species

Abstract

Oligodeoxyribonucleotides containing 8-hydroxyguanine and 2-hydroxyadenine, purine lesions produced in cells by reactive oxygen species, were synthesized and inserted into vector DNAs to introduce each lesion at a predetermined site. The manipulated DNAs were transfected into living cells, and the mutants induced by each DNA lesion were collected and analyzed. In addition, the mutations induced by damaged DNA precursors with the two oxidized purine bases were studied by the use of chemically synthesized nucleoside triphosphates. In this review article, the author summarizes the mutagenic potentials of the two oxidized purine bases, by focusing on experiments examined by the author and his collaborators.

Roles of specialized DNA polymerases in mutagenesis by 8-hydroxyguanine in human cells

“…8-Hydroxyguanine (8-OH-Gua, 7,8-dihydro-8-oxoguanine) is one of the major oxidized nucleobases produced by ROS, and 100−500 residues are generated per cell per day [1][2][3].…”

Involvement of specialized DNA polymerases in mutagenesis by 8-hydroxy-dGTP in human cells

“…The resulting nucleic acid oxidation represents a potentially important source of mutations, and is one of the causative factors of carcinogenesis, neurodegeneration, and aging [2][3][4]. 8-Hydroxyguanine (8-OH-Gua, also known as 8-oxoguanine) is one of the major oxidized bases produced by reactive oxygen species (ROS) [5,6]. This damaged base has been used as a marker of (DNA) oxidation, due to its sensitive detection by an HPLC-electrochemical detector system [5].…”

Mutagenic effects of 8-hydroxy-dGTP in live mammalian cells

“…8-OH-Gua (also known as 7,8-dihydro-8-oxoguanine) is one of the major oxidized bases [4,5]. Its highly mutagenic potential has been shown by site-directed mutagenesis experiments using Escherichia coli and mammalian cells [6][7][8][9][10][11][12][13][14].…”