• Proceedings of the PSK Conference
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.290.1-290.1
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• 2003

Oxidative DNA damage has been associated with many disease. Quantation of DNA adducts is considered to be a useful biomarker of oxidative DNA damage because its formation can also be induced by oxidative stress. Extensive efforts have been taken to identify the analytical methods for minimizing the artifactual formation of oxidative DNA damage. We have done direct analysis of DNA adducts using LC/ESI-MS without urine sample extraction. (omitted)

• Environmental Analysis Health and Toxicology
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• 제18권4호
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• pp.237-242
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• 2003

Single cell gel electrophoresis (SCGE) was used to the experiment with the variation on the amount of smoking and low dose radiation exposure to find how much the Lymphocyte DNA was damaged, and especially for whom smoke a lot(about 20 or more than 20 cigarettes a day) it was found to be highly damaged. While, the damage of 'not more than 20 cigarettes a day' was found to be not so much significant as like for whom smoke about or more than 20 cigarettes a day And, according to the different amount of the radiation exposure, the Lymphocyte DNA was found to be considerably damaged for 0-13m Sv (P<0.01), it was not able to prove the relationship between the DNA damage and the radiation exposure.

• Molecules and Cells
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• 제42권7호
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• pp.546-556
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• 2019

Protein phosphatase 4 (PP4) is a crucial protein complex that plays an important role in DNA damage response (DDR), including DNA repair, cell cycle arrest and apoptosis. Despite the significance of PP4, the mechanism by which PP4 is regulated remains to be elucidated. Here, we identified a novel PP4 inhibitor, protein phosphatase 4 inhibitory protein (PP4IP) and elucidated its cellular functions. PP4IP-knockout cells were generated using the CRISPR/Cas9 system, and the phosphorylation status of PP4 substrates (H2AX, KAP1, and RPA2) was analyzed. Then we investigated that how PP4IP affects the cellular functions of PP4 by immunoprecipitation, immunofluorescence, and DNA double-strand break (DSB) repair assays. PP4IP interacts with PP4 complex, which is affected by DNA damage and cell cycle progression and decreases the dephosphorylational activity of PP4. Both overexpression and depletion of PP4IP impairs DSB repairs and sensitizes cells to genotoxic stress, suggesting timely inhibition of PP4 to be indispensable for cells in responding to DNA damage. Our results identify a novel inhibitor of PP4 that inhibits PP4-mediated cellular functions and establish the physiological importance of this regulation. In addition, PP4IP might be developed as potential therapeutic reagents for targeting tumors particularly with high level of PP4C expression.

• YAKHAK HOEJI
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• 제54권6호
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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.

• The Korean Journal of Physiology and Pharmacology
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• 제1권2호
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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 $TNF{\alpha}$.

• The Korean Journal of Food And Nutrition
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• 제33권3호
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• pp.309-316
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• 2020

In this study, we investigated the protective effects of Ulva lactuca methanol extracts against ultraviolet B (UVB)-induced DNA damage in HaCaT cells. First, the contents of general and antioxidative nutrient contents of Ulva lactuca were measured. The moisture, carbohydrate, crude protein, crude fat and ash were 14.01%, 44.80%, 23.19%, 3.10% and 14.90%, respectively. Magnesium that acts as DNA repair enzyme cofactor was the most abundant mineral followed by Ca, P and Fe. The total phenolic and anthocyanoside contents of Ulva lactuca were 2.69 mg/g and 0.13 mg/g, respectively. Cells treated with Ulva lactuca methanol extracts for 24 hours post UVB exposure increased cell viability in a concentration-dependent manner compared to the non-treated control. Also, Ulva lactuca methanol extracts decreased the levels of UVB-induced DNA damage such as cyclobutane pyrimidine dimer and DNA damage response (DDR) proteins such as p-p53 and p21. These results suggest that Ulva lactuca methanol extracts comprising physiological active substances such as Mg, polyphenols and anthocyanosides promote DNA repair by regulating genes related with DDR.

• Molecules and Cells
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• 제27권5호
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• pp.557-562
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• 2009

We examined the effects of the NADPH oxidase p22phox C242T polymorphism on endurance exercise performance and oxidative DNA damage in response to acute and chronic exercises. One hundred three subjects were recruited, among which 26 healthy subjects (CC: 12, TC: 12, and TT: 2) were studied during rest, exercise at 85% $VO_2max$, and recovery before and after 8 weeks of treadmill running. Lymphocyte DNA damage increased significantly in response to exercise (p < 0.05). There were no significant differences in plasma MDA, SOD concentrations and lymphocyte DNA damage between CC genotype and T allele group, but significant endurance training differences were observed. Endurance training increased exercise time to exhaustion in both the CC genotype and T allele groups (p < 0.05) but no significant difference was found between groups. The results of the current study with young, healthy, Korean men are interpreted to mean that 1) the majority had the CC genotype of the NADPH oxidase p22phox C242T polymorphism (82.5%: CC, 15.5%: TC, 1.9%: TT), 2) acute exercise increased lymphocyte DNA damage, 3) endurance training significantly increased exercise time to exhaustion, and alleviated lymphocyte DNA damage, and 4) The NADPH oxidase p22phox C242T polymorphism, however, did not alter lymphocyte DNA damage or exercise performance at rest, immediately after exercise, or during recovery.

• Journal of Radiation Protection and Research
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• 제40권2호
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• pp.87-91
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• 2015

We have employed X-ray photoelectron spectroscopy (XPS) technique to examine the combined effects of low-energy electron (LEE) irradiation and $Fe^{3+}$ ion on DNA damage. pBR322 plasmid DNA extracted from E. coli ER2420 was used for preparing DNA-$Fe^{3+}$ sample. The C1s XPS spectra were scanned for LEE-irradiated and LEE-unirradiated samples and then curve-fitted. For the samples with LEE irradiation only or with Fe ion only, no significant changes from pure DNA samples were observed - a single effect of either $Fe^{3+}$ ion or LEE irradiation did not cause a significant damage. However, when these two components were combined, the DNA damage was increased quite significantly, compared to the sum of DNA damages caused by $Fe^{3+}$ ion and by LEE irradiation independently. This observation is consistent with our previous results [Radiat. Res. 177, 775 (2012)] which was done using gel-electrophoresis technique. Partial interpretation of the observed spectrum peaks was also attempted.

• Journal of Veterinary Clinics
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• 제22권1호
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• pp.36-42
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• 2005

Lots of waste are produced from cities and embeded at the depository. The waste produces chemicals and organic matters. Those toxicants contaminate air and water. The pollution causes the increase of insects thereby to spray pesticide on the depository as well as its outskirts. Chemicals and pesticide ingredients are accumulated on the depository and released into outskirts. Those toxic agents are assumed to generate DNA damage to animals exposed to the water and air pollutions. To prove the possibility of DNA damage to pollution, comet assay was conducted on lymphocytes of animals exposed to the pollution of a depository at Southern part of Seoul. Peripheral lymphocytes of animals were treated with endonuclease III and electrophoresed. Broken DNA was released and measured under fluorescence microscope. The measurement showed no statistically significant DNA damage but some individuals showed higher DNA damage than in that of control group. These experiments were carried out on rabbits and dogs, the most and the least contaminated, respectively. The rate of DNA damage of cows was in between that of rabbits and dogs.

• Biomolecules & Therapeutics
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• 제19권3호
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• pp.282-287
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• 2011

Sirt1, a nicotinamide adenine dinucleotide ($NAD^+$)-dependent histone deacetylase, is known to deacetylate a number of proteins that are involved in various cellular pathways such as the stress response, apoptosis and cell growth. Modulation of the stress response by Sirtuin 1 (Sirt1) is achieved by the deacetylation of key proteins in a cellular pathway, and leads to a delay in the onset of cancer or aging. In particular, Sirt1 is known to play an important role in maintaining genomic stability, which may be strongly associated with a protective effect during tumorigenesis and during the onset of aging. In these studies, Sirt1 was generated in stably expressing cells and during the stimulation of DNA damage to examine whether it promotes survival. Sirt1 expressing cells facilitated the repair of DNA damage induced by either ionizing radiation (IR) or bleomycin (BLM) treatment. Fastened damaged DNA repair in Sirt1 expressing cells corresponded to prompt activation of Chk2 and ${\gamma}$-H2AX foci formation and promoted survival. Inhibition of Sirt1 enzymatic activity by a chemical inhibitor, nicotinamide (NIC), delayed DNA damage repair, indicating that promoted DNA damage repair by Sirt1 functions to induce survival when DNA damage occurs.