• Title/Summary/Keyword: Damaged DNA

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Analysis of the global gene expression profiles in genomic instability-induced cervical cancer cells

  • Oh, Jung-Min
    • International Journal of Oral Biology
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    • v.47 no.2
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    • pp.17-24
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    • 2022
  • Preserving intact genetic material and delivering it to the next generation are the most significant tasks of living organisms. The integrity of DNA sequences is under constant threat from endogenous and exogenous factors. The accumulation of damaged or incompletely-repaired DNA can cause serious problems in cells, including cell death or cancer development. Various DNA damage detection systems and repair mechanisms have evolved at the cellular level. Although the mechanisms of these responses have been extensively studied, the global RNA expression profiles associated with genomic instability are not well-known. To detect global gene expression changes under different DNA damage and hypoxic conditions, we performed RNA-seq after treating human cervical cancer cells with ionizing radiation (IR), hydroxyurea, mitomycin C (MMC), or 1% O2 (hypoxia). Results showed that the expression of 184-1037 genes was altered by each stimulus. We found that the expression of 51 genes changed under IR, MMC, and hypoxia. These findings revealed damage-specific genes that varied differently according to each stimulus and common genes that are universally altered in genetic instability.

Effects of Radioprotectors on DNA Repair Capacity of Tumor Cells

  • Kim, Choon-Mi;Kim, Mi-Kyung
    • Archives of Pharmacal Research
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    • v.16 no.4
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    • pp.259-264
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    • 1993
  • Three cell lines, CHO, L929 and B16 which are non-tumorigenic and cancer cells, respectively, were first tested for their survival in the presence of radioprotective ginseng protein fraction(GPF0. The influence of three radioprotectors-CPF, cysteamine, and 1-Methyl-2-bis[(2-methylthio)vinyl] quinolinium iodide (MVQI) on DNA repair capacity of UV damaged cells survival test, the GPF showed higher cytotoxicity in L929 and B16 than in CHO cells. However, the degree of cell killing was also investigated by measuring $^3H$-thymidine incorporation of PUVA treated cells. In cell survival test, the GPF showed higher cytotoxicity in L929 and B16 than in CHO cells. However, the degree of cell killing was not high enough to consider it as an antitumorigenic agent. Variable results were obtained in the effects on DNA repair capacity depending on the protectors and cell lines used. In pretreatment, the presence of GPF and MVOI brought about a sinificant increase in the capacity in both CHO and B16 cells. However, in L929, the enhancing effect was not shown. In all three cell lines, cysteamine showed lower repair capacity than control, suggesting the primary damage reduction in stronger enhancing effects in L929 and B16 cells, while it was weaker in CHO cells. Here also cystemine hsowed a very little or no increase in the capacity in all three cell lines. These results demonstrate that GPF has mild cytotoxicity in tumorignic cells and that GPF and MVQI enhance DNA repair capacity of UV damaged cells, whether they are tumorigenic or not. On the other hand, cysteamine shows only damage reduction effect. Celles of different genetic origin seem to give different responses to the modifier and different modifiers may possibly work by different mechanisms.

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Estimation of the Efficiency of Transgenic Rabbit Production Following GFP Gene Microinjection into Rabbit Zygotes

  • Jin, D.I.;Im, K.S.;Kim, D.K.;Choi, W.S.
    • Asian-Australasian Journal of Animal Sciences
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    • v.13 no.10
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    • pp.1367-1372
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    • 2000
  • The present study was conducted to evaluate the efficiency of transgenic rabbit production by DNA microinjection using EGFP (Enhanced Green Fluorescent Protein) gene. In this experiment EGFP coding sequences fused to CMV promoter were microinjected into rabbit one-cell embryos, and then GFP expression and gene integration were evaluated in preimplantation embryos and fetuses recovered on day 15 of pregnancy to determine efficiency of transgenic rabbit production. Effect of DNA concentration was also tested on development in vitro following microinjection and transgene integration in fetuses. Development of embryos in vitro was decreased by DNA microinjection, but the rates of pregnancy and implantation were not significantly affected by microinjection. As development progressed in vitro percentage of GFP expression in rabbit embryos was decreased, resulting GFP expression detected in 37.5% of blastocysts. The efficiencies for production of transgenic fetuses were 4.0% and 7.6%, respectively, when $10ng/{\mu}l$ and $20ng/{\mu}l$ of DNA concentration were microinjected. Transgenic fetuses were confirmed by GFP expression and PCR analysis of fetus genomic DNA. These results indicated that DNA microinjection itself damaged embryo development and DNA concentration affected the efficiency of transgenic rabbit production.

Buddleja officinalis prevents the normal cells from oxidative damage via antioxidant activity

  • Hong, Se-Chul;Jeong, Jin-Boo;Jeong, Hyung-Jin
    • Korean Journal of Plant Resources
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    • v.21 no.6
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    • pp.449-456
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    • 2008
  • The flowers of Buddleja officinalis are used to treat sore and damaged eyes, a condition which is similar to skin wounds. However, whether it has any protective effect on oxidative DNA damage and cell death induced by hydroxyl radical remains unclear. In this study, we evaluated the protective effects of the extracts against oxidative DNA and cell damage caused by hydroxyl radical. DPPH radical, hydroxyl radical, hydrogen peroxide and intracellular ROS scavenging assay, and $Fe^{2+}$ chelating assay were used to evaluate the antioxidant properties. phi X 174 RF I plasmid DNA and intracellular DNA migration assay were used to evaluate the protective effect against oxidative DNA damage. Lastly, MTT assay and lipid peroxidation assay were used to evaluate the protective effect against oxidative cell damage. It was found to prevent intracellular DNA and the normal cells from oxidative damage caused by hydroxyl radical via antioxidant activities. These results suggest that Buddleja officinalis may exert the inhibitory effect on ROS-induced carcinogenesis by blocking oxidative DNA damage and cell death.

Effects of Anti-Neoplastic Antibiotics on DNA Replication and Repair (DNA복제 및 회복에 미치는 수종항암 항생제의 영향에 관한 연구)

  • Park, Sang-Dai;Rie, Myung-Chull;Lee, Chun-Bok
    • The Korean Journal of Zoology
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    • v.26 no.1
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    • pp.19-28
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    • 1983
  • Alkaline elution profiles showed that the frequency of DNA single strand breaks associated with DNA-protein crosslinks in cells treated with both an inducing dose of MMC $(MMC_1)$ and a challenge dose of MMC $(MMC_2)$ was slightly less than that in cells treated with MMC alone. The amount of unscheduled DNA synthesisi in cells treated with both $MMC_1$ and $MMC_2$ was greater than that in cells treated with MMC alone. This enhancement of exicision repair detected by UDS autoradiography and alkaline elution, was not observed, when cells were incubated with cyclohexmide between the two treatments of $MMC_1$ and $MMC_2$. These results suggest that MMC-damaged DNA from Chinses hamster cells is repaired by excision repair mechanisms that require de novo protein synthesis for enhancement, and that an inducible repair mechanism may exist in CHO cells.

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The DNA Damage by Linoleic Acid Hydroperoxide (Linoleic acid과산화물의 DNA 손상작용)

  • KIM Seon-Bong;KANG Jin-Hoon;BYUN Han-Seok;KIM In-Soo;PARK Yeung-Ho
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.20 no.6
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    • pp.569-572
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    • 1987
  • The DNA damage by linoleic acid hydroperoxide (LHPO) was investigated in a DNA-LHPO system at $37^{\circ}C$ to elucidate the DNA damage mechanism by lipid peroxidation products. LHPO shelved a great DNA damage with the increase of its concentrations. DNA was completely damaged in a LHPO-DNA(weight ratio, 2:3) system after incubation for 2 days. The degree of DNA ,damage by LHPO was greated than that of linoleic acid. In the quantitative analysis of DNA damage, the decreasing ratio of DNA content was $60\%$ in $84{\mu}g$ LHPO system incubated for 1 day compared to the control solution marked $30\%$. There were no participation of active oxygens on the DNA damage by LHPO.

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Molecular Dynamics Simulation of Intercalation of Benzopyrene Motif in DNA (핵산의 분자역학적 모의실험을 통한 벤조피렌 층상구조의 발현)

  • Park, Kyung-Lae;Santos, Carlos De Los
    • YAKHAK HOEJI
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    • v.54 no.1
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    • pp.62-66
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    • 2010
  • Benzopyrene is known to be one of the most powerful carcinogens which can build intercalated motif between base pairs in damaged DNA. The dimension of benzopyrene itself is much bigger than any of the DNA bases and thus the question whether the lesion of some base pair by insertion of benzopyrene can happen with or without a dramatic distortion of the helical structure is a highly interesting theme. In this work we used a molecular mechanics simulation using AMBER program package to go into the conformational characteristics. The condition of the insertion process of the benzopyrene motif from minor groove of the starting structure between the base pairs in the internal area of double helix was investigated using the molecular dynamics simulation at elevated temperature.

Tissue-specific expression of DNA repair gene, N-methylpurine-DNA glycosylase (MPG) in Balb/c mice without external damage

  • Kim, Nam-Keun;Lee, Sook-Hwan;Ko, Jung-Jae;Roy, Rabindra;Lee, Hey-Kyung;Kwak, In-Pyung;Cha, Kwang-Yul
    • Journal of Genetic Medicine
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    • v.2 no.1
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    • pp.31-34
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    • 1998
  • The N-methylpurine-DNA glycosylase (MPG), a ubiquitous DNA repair enzyme, removes N-methylpurine and other damaged purines induced in DNA. Tissue-specific mRNA levels of the N-methylpurine-DNA glycosylase (MPG) were investigated in Balb/c mice of four different growing stages; newborn, 1, 4 and 8-weeks postpartum. MPG expressions in the newborn and the 8-week-old mice were the highest in thymus and testis, respectively. The tested tissues of the newborn mice had consistently higher MPG mRNA level than 8-week-old adults except in testis and thymus. The MPG mRNA level in testis was the lowest in the newborn mice, but it attained the highest in the 8-week-old mice. The levels of MPG mRNA among the different tissues in the newborn and the 8-week-old mice were more than 9.0 and 19.0-fold respectively. These results suggest that the of MPG expression was dependent on the growing stage and had tissue-specificity.

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Anti-oxidative effects of Phellinus linteus and red ginseng extracts on oxidative stress-induced DNA damage

  • Park, Byung-Jae;Lim, Yeong-Seok;Lee, Hee-Jung;Eum, Won-Sik;Park, Jin-Seu;Han, Kyu-Hyung;Choi, Soo-Young;Lee, Kil-Soo
    • BMB Reports
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    • v.42 no.8
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    • pp.500-505
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    • 2009
  • Anti-oxidative effect of Phellinus linteus (P. linteus) and red ginseng extracts on DNA damage induced by reactive oxygen species (ROS) were investigated in this study. P. linteus (PLE) and red ginseng extracts (RGE) inhibited the breaking of E. coli ColE1 plasmid DNA strands as well as nuclear DNA of rat hepatocytes damaged by oxidative stress. In addition, a reaction mixture of PLE and RGE showed synergistic inhibitory effect against DNA damage. These results suggest that PLE and RGE have a cellular defensive effect against DNA damage induced by ROS.

DNA-Breaking Action of Some Biologically Active and Other Nitrogen Compounds (수종(數種)의 생리활성물질(生理活性物質) 및 함질소화합물(含窒素化合物)의 DNA 절단작용(切斷作用))

  • Lee, Jin Ha;Ham, Seung Si
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.12 no.4
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    • pp.305-309
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    • 1983
  • The effect of the nucleic acid related compounds, amino acids and ureas on the breakage of calf thymus DNA were investigated with or without inorganic salts. PTU and Cys-SH possessed the ability of DNA strand breaks without metal ions. Tyr, Phe and Trp induced a weak DNA lesions in the presence of $CuSO_4$. Cys-SH with concentrations of 5mM in the presence of metal ion, $CuSO_4$, showed the strong ability to break the DNA. Various metal solutions($500{\mu}M$) except $Sn^{2+}$ did not show the DNA-breaking action. The DNA strands were damaged by some amino acids in the presence of $Cu^{2+}$, $Ni^{2+}$, $Mn^{2+}$, $Zn^{2+}$ and $Sn^{2+}$.

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