Mutagenic potentials of damaged nucleic acids produced by reactive oxygen/nitrogen species: approaches using synthetic oligonucleotides and nucleotides: SURVEY AND SUMMARY

Kamiya, Hiroyuki

doi:10.1093/nar/gkg137

Cited by 249 publications

(226 citation statements)

References 133 publications

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“…For these reasons, ROS and the resulting DNA oxidation represent a potentially important source of mutations and one of the causative factors of carcinogenesis, neurodegeneration, and aging [1][2][3]. 8-OH-Gua (also known as 7,8-dihydro-8-oxoguanine) is one of the major oxidized bases [4,5].…”

Section: Introductionmentioning

confidence: 99%

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

Satou

Kawai

Kasai

et al. 2007

Free Radical Biology and Medicine

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The mutagenicity of an oxidized form of dGTP, 8-hydroxy-2'-deoxyguanosine 5'-triphosphate (8-OH-dGTP), was examined using COS-7 cells. 8-OH-dGTP and supF shuttle plasmid DNA were co-introduced by means of cationic liposomes, and the DNAs replicated in the cells were recovered and then transfected into Escherichia coli. These results constitute the first direct evidence to show that 8-OH-dGTP actually induces mutations in living mammalian cells. 8-OH-dGTP induced

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Section: Introductionmentioning

confidence: 99%

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

Satou

Kawai

Kasai

et al. 2007

Free Radical Biology and Medicine

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“…Moreover, the knock-downs of DNA pol η slightly reduced the mutations induced by 8-OH-Gua paired with A. In addition to DNA pols, DNA repair enzymes and nucleotide pool sanitization enzymes would play important roles in the mutagenesis processes of damaged DNA and DNA precursors [54]. Experiments to reveal their roles are currently in progress.…”

mentioning

confidence: 99%

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

Kamiya

Yamaguchi

Suzuki

et al. 2010

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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“…The formation of ROS leads to the oxidation of cellular components and disturbs their normal functions. The formation of oxidized DNA lesions is one of the causative factors of mutagenesis, carcinogenesis, neurodegeneration, and aging [1][2][3][4][5].…”

mentioning

confidence: 99%

Suppression of mutagenesis by 8-hydroxy-2′-deoxyguanosine 5′-triphosphate (7,8-dihydro-8-oxo-2′-deoxyguanosine 5′-triphosphate) by human MTH1, MTH2, and NUDT5

Hori

Satou

Harashima

et al. 2010

Free Radical Biology and Medicine

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To assess the functions of the three human MutT-type enzymes, MTH1, MTH2, and NUDT5, mutation induction by an oxidized form of dGTP, 8-hydroxy-2'-deoxyguanosine 5'-triphosphate (8-OH-dGTP, 7,8-dihydro-8-oxo-2'-deoxyguanosine 5'-triphosphate), was examined using human 293T cells treated with their specific siRNAs. Shuttle plasmid DNA containing the supF gene was first transfected into the cells, and then 8-OH-dGTP was introduced by means of osmotic pressure. Escherichia coli cells were transformed with the DNAs replicated in the treated cells.The knock-downs of the MTH1, MTH2, and NUDT5 proteins increased the A:TC:G substitution mutations induced by 8-OH-dGTP. In addition, the increase in the induced mutation frequency was more evident in the triple knock-down cells. These results indicate that all three of the human MTH1, MTH2, and NUDT5 proteins act as a defense against the mutagenesis induced by oxidized dGTP. 3Normal cellular metabolism produces endogenous reactive oxygen species (ROS). ROS are generated as byproducts of the mitochondrial electron transport chain, and certain cellular enzymes also generate ROS.Moreover, ROS are produced by environmental mutagens/carcinogens, including ionizing radiation and ultraviolet light. The formation of ROS leads to the oxidation of cellular components and disturbs their normal functions. The formation of oxidized DNA lesions is one of the causative factors of mutagenesis, carcinogenesis, neurodegeneration, and aging [1][2][3][4][5].DNA precursors (2'-deoxyribonucleotides) are also subjected to oxidative damage. The formation of oxidized DNA precursors is a potential source of mutagenesis [6]. 8-Hydroxy-2'-deoxyguanosine 5'-triphosphate (8-OH-dGTP, 7,8-dihydro-8-oxo-2'-deoxyguanosine 5'-triphosphate) is the major oxidation product of dGTP in in vitro oxidation reactions [7].8-OH-dGTP was reportedly present at a concentration of 1-10% relative to the unmodified dGTP in the mitochondrial nucleotide pool [8]. This oxidized form of dGTP is highly mutagenic in living cells when added exogenously [9][10][11] and is expected to act as an endogenous mutagen.Nucleotide pool sanitization is an important means by which organisms prevent the mutagenesis caused by damaged DNA precursors [6,12] Mutagenesis experiments293T cells (3 X 10 4 cells) were plated into 24-well dishes and were cultured in Dulbecco's modified Eagle medium supplemented with 10% fetal calf serum, at 37°C under a 5% CO 2 atmosphere for 24 hr. siRNAs (7.2 pmol each) were mixed with Lipofectamine (Invitrogen) and introduced into the cultured 293T cells according to the supplier's recommendations. In the triple knock-down experiment, an siRNA cocktail (MTH1; 3.6 pmol, MTH2; 7.2 pmol and NUDT5; 3.6 pmol) was used.After 24 Quantitative RT-PCR analysis of mRNATotal RNA was extracted from 293T cells using an RNeasy Mini Kit (Qiagen) combined with RNase-free DNase I (Takara, Otsu, Japan), for the degradation of the genomic DNA in the total RNA samples. First-strand cDNA synthesis was performed with 500 ng of t...

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Mutagenic potentials of damaged nucleic acids produced by reactive oxygen/nitrogen species: approaches using synthetic oligonucleotides and nucleotides: SURVEY AND SUMMARY

Cited by 249 publications

References 133 publications

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

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

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

Suppression of mutagenesis by 8-hydroxy-2′-deoxyguanosine 5′-triphosphate (7,8-dihydro-8-oxo-2′-deoxyguanosine 5′-triphosphate) by human MTH1, MTH2, and NUDT5

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