• Title/Summary/Keyword: 8-hydroxydeoxyguanosine

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G1 CELL CYCLE ARREST OF KG-1, A HUMAN ACUTE LEUKEMIA CELLS, BY 8-HYDROXYDEOXYGUANOSINE OCCURS THROUGH BLOCKADE OF THE EXTRACELLULAR SIGNAL REGULATED KINASE PATHWAY

  • Hyun, Jin-Won;Yoon, Sun-Hee;Yoon, Byung-Hak;Chung, Myung-Hee
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.11b
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    • pp.138-138
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    • 2002
  • 8-hydroxydeoxyguanosine (oh8dG) potently inhibits proliferation of KG-1, a human leukemia cell line in vitro, but little is known regarding to molecular mechanisms mediating this effect. Here we demonstrate that treatment of KG-1, deficient in 8-oxoguanine glycosylase (OGG1) activity, with oh8dG lead to G1 arrest associated with a dramatic decrease in the levels of cyclin D3 and cyclin-dependent kinase 4 (cdk4) and accompanied by an increase in the expression of p21.(omitted)

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Effect of ALDH2 Enzyme Activity on the Level of 8-Hydroxydeoxyguanosine in Tissues Following Ethanol Exposure (ALDH2 효소의 활성이 알코올 섭취에 의한 8-hydroxydeoxyguanosine의 장기별 농도에 미치는 영향)

  • Zhang, Yan Wei;Choi, Sheung-Hee;Kim, Yun-Sik;Moon, Sun-In;Eom, Sang-Yong;Kim, Yong-Dae;Kim, Heon
    • Journal of Life Science
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    • v.18 no.8
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    • pp.1173-1176
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    • 2008
  • Individuals who regularly consume excessive quantities of alcohol are at a greater risk of developing various cancers such as esophageal, pharyngeal and lung cancers compared to normal populations if they are deficient in ALDH2 enzyme activity. We evaluated oxidative DNA damage in the liver, brain, and lung tissues of Aldh2 +/+ and Aldh2 -/- mice after they had been subjected to acute ethanol exposure. The 8-hydroxydeoxyguanosine (8-OHdG) level in each tissue was evaluated as a biomarker of oxidative DNA damage. The 8-OHdG level in the liver, brain, and lung tissues was significantly increased following ethanol treatment. In addition, the level of 8-OHdG in the liver and lung tissues was affected by ALDH2 enzyme activity. This result suggests that ALDH2-deficient individuals may be more susceptible than wild-type ALDH2 individuals to ethanol-mediated diseases, including cancer.

The Relationship between the Urinary Arsenic and 8-Hydroxydeoxyguanosine Levels in Women of Abandoned Mine Area (일부 폐금속광산 지역 거주 여성의 요중 비소와 8-hydroxydeoxyguanosine 농도 사이의 관련성)

  • Choi, Young-Sook;Eom, Sang-Yong;Choi, Byoung-Sun;Park, Jung-Duk;Kim, Yong-Dae;Kim, Heon
    • Journal of Life Science
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    • v.20 no.4
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    • pp.618-622
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    • 2010
  • This study examines the relationship between urinary arsenic concentration and urinary 8-hydroxydeoxyguanosine (8-OHdG) concentrations, an index of oxidative DNA damage, among women who live near abandoned metal mines. The sample consisted of 165 residents living near two abandoned metal mines located in Chungbuk Province. Demographic characteristics as well as environmental factors relevant to arsenic exposure were collected through interviews, and urinary arsenic concentrations and urinary 8-OHdG concentrations of the research subjects were measured. The collected data were subsequently analyzed using the statistics program SPSS 12.0. The geometric average of urinary arsenic concentrations among the research subjects was $5.65\;{\mu}g/g$ creatinine. In a correlation analysis between urinary arsenic and 8-OHdG concentrations, the correlation coefficient was significant (p<0.001) at 0.399. This study suggests that urinary 8-OHdG concentrations may be a DNA damage marker for chronic arsenic exposure in women.

허혈-재관류 심근세포의 DNA에서 8-hydroxydeoxyguanosine 생성

  • 유효진;정명희;김명석;임정규
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1993.04a
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    • pp.82-82
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    • 1993
  • 허혈-재관류손상 심근세포의 DNA에서 8-hydroxydeoxyguanosine (8-OHdG) 생성을 검토하였다. 흰쥐 적출심장의 Langendorff 관류 표본에서 대동맥 차단에 의한 60분 허혈후 산소가 포화된 Kredb-Henseleit용액으로 30분간 재관류 하므로서 허혈-재관류 손상을 유도하였다. 재관류 후 심근세포에서 DNA를 추출하고 HPLC(EC detector)를 이용하여 8-OHdG를 측정하였다. 실험결과 허혈-재관류 심근세포의 DNA에서 8-OHdG 함량이 증가하였으며 이는 $O_2$ 제거물질인 superoxide dismutase와 OH 제거물질인 mannitol에 의하여 방지되었다. Xanthine oxidase외 경쟁적 길항약인 allopurinol도 8-OHdG 생성을 억제하였으며 단백분해효소 억제제인 phenylsulfonylfluoride 그리고 관류액에서 칼슘의 제거 또한 허혈-재관류 심근 DNA의 생성을 방지하였다. 이상의 결과 허혈심근의 재관류시 8-OHdG 생성이 증가하며 이는 재관류 손상과 같은 산화성 심근손상을 평가하는 좋은 Index가 될 수 있을 것으로 여겨진다.

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Effects of Exposure to Hexavalent Chromium on the Level of 8-Hydroxydeoxyguanosine and the Activities of Superoxide Dismutase and 8-Hydroxyguannine Endonuclease in Rat Lung (6가 크롬 폭로가 흰쥐 폐조직의 8-Hydroxydeoxyguanosine 농도 및 Superoxide Dismutase와 8-Hydroxyguanine Endonuclease의 활성에 미치는 영향)

  • Kim, Hun-Sik;Kim, Ro-Sa;Kim, Hyeon-Yeong;Jeong, Jae-Hwang;Kim, Heon
    • Journal of Preventive Medicine and Public Health
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    • v.32 no.1
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    • pp.101-107
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    • 1999
  • Objectives. To determine the effects of exposure to hexavalent chromium, 93 male Sprague-Dawley rats were exposed to hexavalent chromium solution. Methods. Rats were divided into 4 groups and exposed to 0.1ml of 0 mM, 0.4 mM, 2.0 mM, and 10.0 mM potassium chromate in the first experiment, and to 0.1 ml of 0 mM, 20 mM, 40 mM, and 80 mM in the second for consecutive 3 days by tracheal instillation. Three and 10 rats were the controls for the first and the second experiments, respectively. Lung tissues were then removed to measure the 8-hydroxydeoxyguanosine (8-OH-dG) level using the HPLC-ECD method, superoxide dismutase (SOD) activity using the cytochrome C method, and 8-hydroxyguanine endonuclease activity using the oligonucleotide nicking assay. Results. The results showed no significant linear relationship between chromium exposure level and 8-OH-dG level or 8-hydroxyguanine endonuclease activity. In the first experiment, 8-OH-dG level and 8-hydroxyguanine endonuclease activity increased in 0.4 mM group, and then decreased in 2.0 mM and 10.0 mM groups. The correlation coefficients between 8-OH-dG level and 8-hydroxyguanine endonuclease activity was statistically significant (P<0.01), and total SOD activity was elevated by chromium exposure in a dose-dependent manner (P<0.05). In contrast, there was no significant dose-response pattern or correlation in the secod experiment. Conclusions. Based on the fact that there was no linear relationship between chromium dose and 8-OH-dG level or activity of the repair enzyme, it seems unlikely that 8-OH-dG formation is the major mechanism of chromium carcinogenesis.

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Effects of Hyperoxia on 8-Hydroxydeoxyguanosine Formation in Carbon Monoxide Exposed Rats (일산화탄소 중독시 고압산소투여가 8-hydroxydeoxyguanosine 생성에 미치는 영향)

  • Kim, Heon;Cho, Soo-Hun;Chung, Myung-Hee
    • Journal of Preventive Medicine and Public Health
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    • v.27 no.1 s.45
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    • pp.84-106
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    • 1994
  • Hyperbaric oxygen (HBO) therapy for carbon monoxide (CO) poisoning eventually inducing the hypoxia-reoxygenation condition, may produce oxygen free radicals, which forms 8-hydroxydeoxyguanosine (8-OH-dG) by attacking C-8 position of deoxyguanosine (dG) in DNA. Effects of oxygen partial pressure or duration of HBO therapy with or without CO poisoning on the tissue 8-OH-dG formation were investigated. Male Sprague-Dawley rats were grouped and exposed to air (control group), 4000 ppm of CO for 10 to 30 minutes (CO only group), air for 30 minutes after 30 minute exposure to 4000 ppm of CO(CO-air exposure group), HBO after 30 minute exposure to 4000 ppm of CO(CO-HBO group), or HBO therapy fo. $10{\sim}120$ minutes(HBO only group). The 8-OH-4G concentrations in the brain and the lung tissues were measured with high performance liquid chromatography and electrochemical detector (ECD). Average concentrations of the 8-OH-dG of each group were statistically compared. In the brain tissues, 8-OH-dG concentrations of the CO only group, the CO-air exposure group, and the CO-HBO group did not significantly differ from those of the control group. Similar insignificance was also found between the CO-HBO group and the HBO only groups. No appreciable dose-response relationship was observed between the 8-OH-dG concentration and the oxygen partial pressure or the duration of HBO. However, the 8-OH-dG concentrations of the 30 minute CO only group were higher than those of the CO-air exposure group (p-value<0.05). In the lung tissues, there were no significant differences between the 8-OH-dG concentrations of the control group and those of the CO only group, the CO-air exposure group, and the CO-HBO group. However, mean 8-OH-dG concentration of the CO-air exposure group was significantly higher than that of the CO only group under the same CO exposure condition(p-value<0.05). With the duration of CO exposure, the 8-OH-dG concentrations of the lung tissues decreased significantly (p-value<0.05). The concentrations of 8-OH-dG in the lung tissues proportionally increased with the duration of HBO, but no such relation was observed with the oxygen partial pressure. These results suggest that the brain may be more resistant to oxygen free radicals as compared with the lungs, and that oxygen toxicity following HBO may be affected by factors other than oxygen free radicals.

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The Relationship between Urinary 8-hydroxydeoxyguanosine and Polycyclic Aromatic Hydrocarbons Exposure in Working Environment

  • Lee Jong-Seong;Kim Eun-A;Lee Yong-Hag;Moon Deog-Hwan;Kim Kwang-Jong
    • Biomedical Science Letters
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    • v.11 no.2
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    • pp.143-152
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    • 2005
  • To investigate the exposure effect of polycyclic aromatic hydrocarbons (PAHs), we analyzed the relationship between urinary 8-hydroxydeoxyguanosine (8-OHdG) concentration and PAHs exposure. The study population contained 44 workers in steel-pipe coating and paint manufacture industries. We measured airborne total PAHs as an external dose, urinary 1-hydroxypyrene (1-OHP) as an internal dose of PAHs exposure, and urinary 8-OHdG as an effective dose of oxidative DNA damage. There was significant correlation between the urinary concentration of l-OHP and the environmental concentration of PAHs, pyrene, urinary cotinine, AST, and GGT. The mean of urinary 8-OHdG was $17.07\pm1.706{\mu}g/g$ creatinine in workers exposed to airborne PAHs. There was significant correlation between the urinary concentration of 8-0HdG and the airborne concentration of PAHs. From the results of stepwise multiple regression analysis about 8-OHdG, significant independents was total PAHs. In this study, there were significant correlation between the urinary concentration of 8-OHdG and the airborne concentration of PAHs. The urinary 1-OHP was effective index as a biomarker of airborne PAHs in workplace. But it was influenced by non-occupational PAHs source, smoking and biomarkers of liver function test.

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