Repair System of 7, 8-Dihydro-8-Oxoguanine as a Defense Line against Carcinogenesis

Hirano, Takeshi

doi:10.1269/jrr.08049

Cited by 69 publications

(60 citation statements)

References 91 publications

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“…Low serum, plasma or urine levels of 8-oxodG can be a sign of enfeebled repair of oxidatively damaged DNA or enhanced antioxidant defence rather than low ROS production. The main repair enzyme for 8-oxodG is human 8-oxoguanine DNA glycosylase 1 (hOGG1) and its proper function is crucial for the prevention of G to T transversion mutations (Hirano, 2008). Reduced hOGG1 levels significantly increase relative risk for initiation of carcinomas (Paz-Elizur et al, 2003.…”

Section: Discussionmentioning

confidence: 99%

8-Hydroxydeoxyguanosine: a new potential independent prognostic factor in breast cancer

et al. 2010

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BACKGROUND: is the commonly used marker of oxidative stress-derived DNA damage. 8-OxodG formation is regulated by local antioxidant capacity and DNA repair enzyme activity. Earlier studies have reported contradictory data on the function of 8-oxodG as a prognostic factor in different cancer types. METHODS: We assessed pre-operative serum 8-oxodG levels with an enzyme-linked immunosorbent assay in a well-defined series of 173 breast cancer patients. 8-OxodG expression in the nuclei of cancer cells from 150 of these patients was examined by immunohistochemistry. RESULTS: The serum 8-oxodG levels and immunohistochemical 8-oxodG expression were in concordance with each other (Po0.05). Negative 8-oxodG immunostaining was an independent prognostic factor for poor breast cancer-specific survival according to the multivariate analysis (Po0.01). This observation was even more remarkable when ductal carcinomas only (n ¼ 140) were considered (Po0.001). A low serum 8-oxodG level was associated statistically significantly with lymphatic vessel invasion and a positive lymph node status. CONCLUSIONS: Low serum 8-oxodG levels and a low immunohistochemical 8-oxodG expression were associated with an aggressive breast cancer phenotype. In addition, negative 8-oxodG immunostaining was a powerful prognostic factor for breast cancer-specific death in breast carcinoma patients.

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Section: Discussionmentioning

confidence: 99%

8-Hydroxydeoxyguanosine: a new potential independent prognostic factor in breast cancer

et al. 2010

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“…How do cells remove a deleterious 8-oxodG incorporated into the nascent strand opposite dA during DNA replication? MutM and Ogg1 recognize and remove 8-oxodG preferentially from 8-oxodG/dC pairs, but they cannot remove 8-oxodG from 8-oxodG/dA pairs (Michaels et al, 1991;Boiteux and Radicella, 1999;Hirano, 2008). Hence, another DNA glycosylase activity must be efficient in removing 8-oxodG from 8-oxodG/dA pairs.…”

Section: Discussionmentioning

confidence: 99%

“…It pairs with dC and dG (Bjelland and Seeberg, 2003;Kamiya, 2004). Base excision repair (BER) is a critical mechanism for preventing mutations by removing the causative damaged bases from DNA (David et al, 2007;Hirano, 2008;Zharkov, 2008). DNA glycosylases hydrolyze the N-glycosylic bond between the oxidized base and deoxyribose, thus releasing a free base and an apurinic/apyrimidinic (AP) site in DNA.…”

Section: Introductionmentioning

confidence: 99%

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CiMutT, an asidian MutT homologue, has a 7, 8-dihydro-8-oxo-dGTP pyrophosphohydrolase activity responsible for sanitization of oxidized nucleotides in Ciona intestinalis

2010

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The oxidized nucleotide precursors 7, 8-dihydro-8-oxo-dGTP (8-oxo-dGTP) and 1, 2-dihydro-2-oxo-dATP (2-oxo-dATP) are readily incorporated into nascent DNA strands during replication, which would cause base substitution mutations. E. coli MutT and human homologue hMTH1 hydrolyze 8-oxo-dGTP, thereby preventing mutations. In this study, we searched for hMTH1 homologues in the ascidian Ciona intestinalis using the NCBI-BLAST database. Among several candidates, we focused on one open reading frame, designated as CiMutT, because of its high degree of identity (41.7%) and similarity (58.3%) to the overall amino acid sequence of hMTH1, including the Nudix box. CiMutT significantly suppressed the mutator activity of E. coli mutT mutant. Purified CiMutT had a pyrophosphohydrolase activity that hydrolyzed 8-oxo-dGTP to 8-oxo-dGMP and inorganic pyrophosphate. It had a pH optimum of 9.5 and Mg ++ requirement with optimal activity at 5 mM. The activity of CiMutT for 8-oxo-dGTP was comparable to that of hMTH1, while it was 100-fold lower for 2-oxo-dATP than that of hMTH1. These facts indicate that CiMutT is a functional homologue of E. coli MutT. In addition, the enzyme hydrolyzed all four of the unoxidized nucleoside triphosphates, with a preference for dATP. The specific activity for 8-oxo-dGTP was greater than that for unoxidized dATP and dGTP. These results suggest that CiMutT has the potential to prevent mutations by 8-oxo-dGTP in C. intestinalis.

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“…It thus eliminates 8-OHG and also forms a nonbasic region via cleavage of the phosphodiester bond with β-elimination reaction (9,10). NEIL endonucleases are homologues of the bacterial MutM/Nei family.…”

Section: Introductionmentioning

confidence: 99%

Effects of Turkish propolis on expression of hOGG-1 and NEIL-1

Turan¹,

Aliyazıcıoğlu²,

Demir³

et al. 2015

Turk J Med Sci

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Background/aim: Propolis is a bee product with antioxidative, antimutagenic, and other beneficial properties, and it is used as a natural drug. It is rich in polyphenolic compounds. Its composition varies depending on the particular geographical region. Oxidative stress is caused by an imbalanced free radical production and antioxidant system. The effects of flavonoids on the expression of DNA repair enzymes have been examined previously; however, no study has investigated the effects of propolis. This study investigated the effects of ethanolic extracts of Turkish propolis (EEP) on the expression of DNA repair enzymes. Materials and methods:The effects of EEP and tertiary-butyl-hydroperoxide (t-BHP) on cell viability were determined using MTT. DNA damage was determined using comet assay. mRNA expression of target enzymes was detected using RT-PCR.Results: According to the cytotoxicity analysis, after a recovery time of 4 h, appropriate damage agent t-BHP and optimum EEP concentrations were 300 µM and 200 µg/mL, respectively. 8-Oxoguanine-glycosylase (hOGG-1) and endonuclease-VIII-like-1 (NEIL-1) expressions increased in the positive control group (t-BHP alone) and the study group (t-BHP+EEP). Maximum increase in NEIL-1 expression was at hour 12 in the positive control group and at hour 8 in the study group. Conclusion:EEP can be considered as a potential source of functional food and pharmaceutical agents.

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Repair System of 7, 8-Dihydro-8-Oxoguanine as a Defense Line against Carcinogenesis

Cited by 69 publications

References 91 publications

8-Hydroxydeoxyguanosine: a new potential independent prognostic factor in breast cancer

8-Hydroxydeoxyguanosine: a new potential independent prognostic factor in breast cancer

CiMutT, an asidian MutT homologue, has a 7, 8-dihydro-8-oxo-dGTP pyrophosphohydrolase activity responsible for sanitization of oxidized nucleotides in Ciona intestinalis

Effects of Turkish propolis on expression of hOGG-1 and NEIL-1

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