• Title/Summary/Keyword: 8-hydroxy2'-deoxyguanosine

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Detection of 8-Hydroxy-2' -Deoxyguanosine in Human Peripheral Blood Leukocytes and Stomach Tissues (사람 백혈구 및 위 조직중의 8-Hydroxy-2'-Deoxyguanosine 측정에 관한 연구)

  • Kang Ho Il;Eom Mi Ok;Park Mi Sun;Ryeom Tai Kyung;Jee Seung Wan;Jeon Hea Myung;Kim Ok Hee
    • Environmental Mutagens and Carcinogens
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    • v.25 no.1
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    • pp.13-18
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    • 2005
  • In the present study, we have measured 8-hydroxy-2'-deoxyguanosine in DNA of stomach cancers, adjacent stomach cancer tissues, normal stomach tissues and peripheral blood leukocytes of the same stomach cancer patients (n = 48) to investigate their etiological association with gastric cancer and possibility whether peripheral blood leukocytes can use surrogate marker for early stomach cancer diagnosis by HPLC/ECD system. In normal stomach tissues, we found that 8-hydroxy-2'-deoxyguanosine levels in tissues infected with Helicobacter pylori were 1.4 fold higher than those in tissues without infected with Helicobacter pylori. However, in adjacent stomach cancer tissues, we found that 8-hydroxy-2'-deoxyguanosine levels in tissues infected with Helicobacter pylori were 1.5 fold lower than those in tissues without infected with Helicobacter pylori. In stomach cancer tissues, 8-hydroxy-2'-deoxyguanosine levels in tissues infected with Helicobacter pylori were not significantly different from those in tissues without infected with Helicobacter pylori. In Helicobacter pylori-negative specimens, 8­hydroxy-2'-deoxyguanosine levels of adjacent stomach cancer tissues were found to be significantly higher than those of normal stomach and cancer tissues. The 8-hydroxy-2'-deoxyguanosine levels of female were 1.7 fold higher than those of male in peripheral blood leukocytes of the same stomach cancer patients. The 8-hydroxy-2'­deoxyguanosine levels in Helicobacter pylori-negative specimens among adjacent stomach cancer tissues were found to be reversely correlated with those in peripheral blood leukocytes, suggesting that 8-hydroxy-2'-deox­yguanosine in peripheral blood leukocytes may not use as surrogate marker for the early diagnosis of human stomach cancer.

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Suppressive Effect of Galangin on the Formation of 8-OH2'dG and DNA Single Strand Breaks by Hydrogen Peroxide ($H_2O_2$ 유도 8-OH2'dG 생성 및 DNA Single Strand Break에 미치는 Galangin의 억제효과)

  • Kim, Soo-Hee;Heo, Moon-Young
    • YAKHAK HOEJI
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    • v.54 no.1
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    • pp.32-38
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    • 2010
  • The aim of this study was to evaluate the effect of galangin towards hydrogen peroxide-induced DNA damage. The calf thymus DNA and Chinese Hamster Lung (CHL) cells were used to measure 8-hydroxy-2'-deoxyguanosine(8-OH2'dG) as an indicator of DNA oxidative damage using high performance liquid chromatography with electrochemical detection. Hydrogen peroxide in the presence of Fe(II) ion induced the formation of 8-OH2'dG in both calf thymus DNA and CHL cells. The DNA damage effects were enhanced by increasing the concentration of Fe(II) ion and inhibited by galangin. In the single cell gel electrophoresis (Comet assay), galangin and dl-a-tocopherol showed an inhibitory effect in CHL on hydrogen peroxide induced DNA single strand breaks. Galangin showed more potent activity than dl-$\alpha$-tocopherol under our experimental conditions. These results indicate that galangin can modify the action mechanisms of the oxidative DNA damage and may act as chemopreventive agents against oxidative stress.

Protective Effect of the 70% Ethanolic Extract of Alpinia officinarum and Galangin Against $KBrO_3$-induced DNA and Chromosomal Damage in Mice (Galangin 및 양강추출물의 $KBrO_3$ 유도 DNA 및 염색체 손상에 대한 보호효과)

  • Yang, Hye-Eun;Heo, Moon-Young
    • YAKHAK HOEJI
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    • v.54 no.6
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    • pp.423-428
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    • 2010
  • The aim of this study was to evaluate the in vivo effect of galangin and the 70% ethanolic extract of Alpinia officinarum (AO) toward $KBrO_3$-induced DNA and chromosomal damage in mice. Galangin and AO inhibited the formation of 8-hydroxy-2'-deoxyguanosine (8-OH2'dG) as an indicator of DNA oxidative damage in the liver cell. Galangin and AO showed the inhibitory effect on the formation of DNA single strand break in the splenocyte by single cell gel electrophoresis (SCGE) assay and also inhibited micronucleated reticulocyte (MNRET) formation of peripheral blood in tail blood of mice. Vit-E revealed antigenotoxic effects in DNA and chromosome levels, but galangin was more potent active compound compare to vit-E under our experimental conditions. The results suggest that the extract of Alpinia officinarum containing galangin can modify the oxidative DNA and chromosomal damage and may act as chemopreventive agent against oxidative stress in vivo.

Evaluation of Antioxidative Activity of Agrimonia pilosa-Ledeb Leaves on Non-lipid Oxidative Damage

  • Hah, Dae-Sik;Kim, Chung-Hui;Kim, Eui-Kyung;Kim, Jong-Shu
    • Toxicological Research
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    • v.25 no.4
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    • pp.243-251
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    • 2009
  • Present study was conducted to evaluate the anti oxidative activity of the Agrimonia pilosa-Ledeb leaves on non-lipid oxidative damage. The antioxidative activity of methanolic (MeOH) extract of the Agrimonia pilosa-Ledeb leaves on non-lipid oxidation, including liposome oxidation, deoxyribose oxidation, protein oxidation, chelating activity against metal ions, scavenging activity against hydrogen peroxide, scavenging activity against hydroxyl radical and 2'-deoxyguanosine (2'-dG) oxidation were investigated. The MeOH extract of the Agrimonia pilosa-Ledeb leaves exhibited high anti oxidative activity in the liposome model system. Deoxyribose peroxidation was inhibited by the MeOH extract of the Agrimonia pilosa-Ledeb leaves and MeOH extract of the Agrimonia pilosa-Ledeb leaves provided remarkable protection against damage to deoxyribose. Protective effect of MeOH extracts of the Agrimonia pilosa-Ledeb leaves on protein damage was observed at $600{\mu}g$ level (82.05%). The MeOH extracts of the Agrimonia pilosa-Ledeb leaves at $300{\mu}g$ revealed metal binding ability (32.64%) for hydrogen peroxide. Furthermore, the oxidation of 2'-deoxyguanosine (2'-dG) to 8-hydroxy-2-deoxyguanosine (8-OH-2'dG) was inhibited by MeOH extracts of the Agrimonia pilosa-Ledeb leaves and scavenging activity for hydroxyl radical exhibited a remarkable effect. From the results in the present study on biological model systems, we concluded that MeOH extract of the Agrimonia pilosa-Ledeb leaves was effective in the protection of non-lipids against various oxidative model systems.

Effects of Resveratrol Supplementation on Oxidative Damage and Lipid Peroxidation Induced by Strenuous Exercise in Rats

  • Xiao, Ning-Ning
    • Biomolecules & Therapeutics
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    • v.23 no.4
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    • pp.374-378
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    • 2015
  • The purpose of the present study was to investigate the effects of resveratrol supplementation on oxidative damage and lipid peroxidation induced by strenuous exercise in rats. The rats were randomly divided into five groups: a sedentary control group, an exercise control group, and three treatment exercise groups administered increasing doses of resveratrol (25, 50, and 100 mg/kg body weight). Resveratrol was administered by oral gavage once daily for four weeks. At the end of the four-week period, the rats performed a strenuous exercise on the treadmill, and the levels of lactate dehydrogenase (LDH), creatine kinase (CK), malondialdehyde (MDA), 4-hydroxy-2-nonenal (4-HNE), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured. The results showed that resveratrol supplementation had protective effects against strenuous exercise-induced oxidative damage and lipid peroxidation by lowering the levels of LDH, CK, MDA, 4-HNE, and 8-OHdG in the serum or muscle of rats. These beneficial effects are probably owing to the inherent antioxidant activities of resveratrol.

The Role of Helicobacter pylori's Fur Protein in the Oxidative Stress Induced by Photodynamic Therapy (Photodynamic Therapy에 의한 산화적 스트레스 조건에서 Helicobacter pylori의 Fur 단백질의 역할)

  • Park, Yu-Na;Kim, Ji-Hoon;Choi, Sung-Sook
    • Korean Journal of Microbiology
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    • v.47 no.2
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    • pp.124-129
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    • 2011
  • The role of the ferric uptake regulator (Fur) of Helicobacter pylori in the oxidative stress was investigated in this study. A fur knockout mutant of H. pylori was constructed by replacing the fur gene with an aphA (kanamycin resistant marker) gene. Photodynamic therapy using methylene blue (MB) and 660 nm light was chosen to induce oxidative stress. The bactericidal effect of photodynamic therapy (PDT) was compared between wild type H. pylori and fur knockout mutant H. pylori. The degree of oxidative damage of DNA was confirmed using alkaline gel electrophoresis and an assay of 8-hydroxy-2-deoxyguanosine (8-OHdG). In control groups, the number of viable cells was maintained constantly during experiment. After PDT, the mutant H. pylori showed 10,000 times decreased viable cell number compared with wild type H. pylori. Depending on the exposure time of 660 nm light, the 3-fold increase in the concentration of 8-OHdG was observed in mutant H. pylori. The results of this study showed that H. pylori's Fur protein may play a role in oxidative stress induced by PDT.

Reduction of TNE ${\alpha}-induced$ Oxidative DNA Damage Product, 8-Hydroxy-2'-Deoxyguanosine, in L929 Cells Stably Transfected with Small Heat Shock Protein

  • Park, Young-Mee;Choi, Eun-Mi
    • The Korean Journal of Physiology and Pharmacology
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    • v.1 no.2
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    • pp.209-219
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    • 1997
  • Previous studies have demonstrated that oxidative stress involving generation of reactive oxygen species (ROS) is responsible for the cytotoxic action of $TNF{\alpha}$. Protective effect of small heat shock proteins (small HSP) against diverse oxidative stress conditions has been suggeted. Although overexpression of small hsp was shown to provide an enhanced survival of $TNF{\alpha}$-sensitive cells when challenged with $TNF{\alpha}$, neither the nature of $TNF{\alpha}$-induced cytotoxicity nor the protective mechanism of small HSP has not been completely understood. In this study, we have attempted to determine whether $TNF{\alpha}$ induces oxidative DNA damage in $TNF{\alpha}$-sensitive L929 cells. We chose to measure the level of 8-hydroxy-2'-deoxyguanosine (8 ohdG), which has been increasingly recognized as one of the most sensitive markers of oxidative DNA damage. Our results clearly demonstrated that the level of 8 ohdG increased in L929 cells in a $TNF{\alpha}$ dose-dependent manner. Subsequently, we asked whether small HSP has a protective effect on $TNF{\alpha}$-induced oxidative DNA damage. To accomplish this goal, we have stably transfected L929 cells with mouse small hsp cDNA (hsp25) since these cells are devoid of endogenous small hsps. We found that $TNF{\alpha}$-induced 8 ohdG was decreased in cells overexpressing exogenous small hsp. We also found that the cell killing activity of $TNF{\alpha}$ was decreased in these cells as measured by clonogenic survival. Taken together, results from the current study show that cytotoxic mechanism of $TNF{\alpha}$ involves oxidative damage of DNA and that overexpression of the small hsp reduces this oxidative damage. We suggest that the reduction of oxidative DNA damage is one of the most important protective mechanisms of small HSP against $TNF{\alpha}$.

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Changes in Urinary MDA and 8-OHdG Concentrations due to Wearing Personal Protective Equipment and Performing Protective Behaviors among Agricultural Workers in Korea (우리나라 일부 농업 종사자의 개인보호구 착용, 작업위생행위에 따른 소변 중 MDA, 8-OHdG 농도 변화)

  • Lee, Jiyun;Ji, Kyunghee;Kim, Bokyung;Park, Seokhwan;Kim, Pan-Gyi
    • Journal of Environmental Health Sciences
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    • v.43 no.6
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    • pp.467-477
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    • 2017
  • Objectives: Oxidative stress and DNA damage have been proposed as mechanisms linking pesticide exposure to health effects such as cancer and neurological diseases. We investigated whether protective measures could significantly reduce the levels of biomarkers for oxidative stress and DNA damage in agricultural workers. Methods: In the present study, the levels of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), biomarkers related to oxidative stress and DNA damage, respectively, were analyzed in urine samples collected from agricultural workers in two provinces of Korea (n=60). The influence of wearing personal protective equipment (PPE) and performing protective behaviors on the levels of these two biomarkers was also evaluated. Results: The median urinary levels of MDA and 8-OHdG were 10.45 nmol/mg creatinine and 14.42 ng/mg creatinine in subjects living in region A, while they were 6.25 nmol/mg creatinine and 24.77 ng/mg creatinine in subjects living in region B, respectively. The levels of MDA and 8-OHdG were higher in male farmers. Farmers wearing greater numbers of PPE and performing more protective behaviors had significantly lower levels of MDA. Greater numbers of protective behaviors was significantly associated with lower levels of 8-OHdG. Conclusion: The results of the present study indicate that pesticide exposure could induce oxidative stress and DNA damage in agricultural workers, and that protective measures are important for mitigating pesticide exposure.

Photodamage to Double-stranded DNA by Xanthone Analogues Increases Exponentially with Their HOMO Energies

  • Hirakawa, Kazutaka;Yoshida, Mami;Oikawa, Shinji;Kawanishi, Shosuke
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.488-490
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    • 2002
  • DNA photodamage mediated by photosensitizers are believed to play an important role in solar UVA carcinogenesis. We investigated the relationship between the DNA-damaging abilities of photoexcited xanthone analogues (as photosensitizers) and their highest occupied molecular orbital (HOMO) energies. DNA damage was examined using /sup 32/P-labeled DNA fragments obtained from the p53 tumor suppressor gene. These compounds induced DNA photodamage in a similar manner, and the extents of DNA damage were following order: xanthone> thioxanthone > acridone. Photoexcited xanthone caused nucleobase oxidation specifically at 5'-G of GG sequence in double-stranded DNA. An oxidative product of 2'-deoxyguanosine, 8-hydroxy-2'-deoxyguanosine (8-OHdG), was detected, and the amount was decreased by DNA denaturation. These findings suggest that photoexcited xanthone generates 8-OHdG at 5'-G of GG in double-stranded DNA through electron transfer. The calculated HOMO energies of these photosensitizers decreased in the following order: xanthone> thioxanthone > acridone. This study has demonstrated that DNA-damaging abilities of these photosensitizers increased exponentially with an increase in their HOMO energies.

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