• Title/Summary/Keyword: DNA damage

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Drosophila melanogaster: a Model for the Study of DNA Damage Checkpoint Response

  • Song, Young-Han
    • Molecules and Cells
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    • v.19 no.2
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    • pp.167-179
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    • 2005
  • The cells of metazoans respond to DNA damage by either arresting their cell cycle in order to repair the DNA, or by undergoing apoptosis. This response is highly conserved across species, and many of the genes involved in this DNA damage response have been shown to be inactivated in human cancers. This suggests the importance of DNA damage response with regard to the prevention of cancer. The DNA damage checkpoint responses vary greatly depending on the developmental context, cell type, gene expression profile, and the degree and nature of the DNA lesions. More valuable information can be obtained from studies utilizing whole organisms in which the molecular basis of development has been well established, such as Drosophila. Since the discovery of the Drosophila p53 orthologue, various aspects of DNA damage responses have been studied in Drosophila. In this review, I will summarize the current knowledge on the DNA damage checkpoint response in Drosophila. With the ease of genetic, cellular, and cytological approaches, Drosophila will become an increasingly valuable model organism for the study of mechanisms inherent to cancer formation associated with defects in the DNA damage pathway.

Effect of Low-Energy Electron Irradiation on DNA Damage by Cu2+ Ion

  • Noh, Hyung-Ah;Park, Yeunsoo;Cho, Hyuck
    • Journal of Radiation Protection and Research
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    • v.42 no.1
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    • pp.63-68
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    • 2017
  • Background: The combined effect of the low energy electron (LEE) irradiation and $Cu^{2+}$ ion on DNA damage was investigated. Materials and Methods: Lyophilized pBR322 plasmid DNA films with various concentrations (1-15 mM) of $Cu^{2+}$ ion were independently irradiated by monochromatic LEEs with 5 eV. The types of DNA damage, single strand break (SSB) and double strand break (DSB), were separated and quantified by gel electrophoresis. Results and Discussion: Without electron irradiation, DNA damage was slightly increased with increasing Cu ion concentration via Fenton reaction. LEE-induced DNA damage, with no Cu ion, was only 6.6% via dissociative electron attachment (DEA) process. However, DNA damage was significantly increased through the combined effect of LEE-irradiation and Cu ion, except around 9 mM Cu ion. The possible pathways of DNA damage for each of these different cases were suggested. Conclusion: The combined effect of LEE-irradiation and Cu ion is likely to cause increasing dissociation after elevated transient negative ion state, resulting in the enhanced DNA damage. For the decrease of DNA damage at around 9-mM Cu ion, it is assumed to be related to the structural stabilization due to DNA inter- and intra-crosslinks via Cu ion.

New Players in the BRCA1-mediated DNA Damage Responsive Pathway

  • Kim, Hongtae;Chen Junjie
    • Molecules and Cells
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    • v.25 no.4
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    • pp.457-461
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    • 2008
  • DNA damage checkpoint is an important self-defense mechanism for the maintenance of genome stability. Defects in DNA damage signaling and repair lead to various disorders and increase tumor incidence in humans. In the past 10 years, we have identified many components involved in the DNA damage-signaling pathway, including the product of breast cancer susceptibility gene 1 (BRCA1). Mutations in BRCA1 are associated with increased risk of breast and ovarian cancers, highlighting the importance of this DNA damage-signaling pathway in tumor suppression. While it becomes clear that BRCA1 plays a crucial role in the DNA damage responsive pathway, exactly how BRCA1 receives DNA damage signals and exerts its checkpoint function has not been fully addressed. A series of recent studies reported the discovery of many novel components involved in DNA damage-signaling pathway. These newly identified checkpoint proteins, including RNF8, RAP80 and CCDC98, work in concern in recruiting BRCA1 to DNA damage sites and thus regulate BRCA1 function in G2/M checkpoint control. This review will summarize these recent findings and provide an updated view of the regulation of BRCA1 in response to DNA damage.

Effect of Antioxidants and Chelating Agents on 1,2,4-benzenetriol-induced DNA damage in HL-60 cells analysed by alkaline comet assay (항산화제 및 금속착화합물이 1,2,4-benzenetriol에 의해 유도된 HL-60 세포의 DNA 손상에 대한 보호 효과)

  • 김선진;정해원
    • Environmental Mutagens and Carcinogens
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    • v.20 no.1
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    • pp.7-13
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    • 2000
  • The mechanisms of benzene toxicity is not fully elucidated, although the metabolism of benzene is very well understood. In order to study the mechanism of benzene toxicity, we investigated DNA damage induced by benzene metabolite, 1,2,4-benzenetriol (BT) in HL-60 cells by alkaline comet assay. To investigate the mechanism of cellular DNA damage induced by BT, the cells were treated with antioxidant such as vitamin C, SOD, catalase, and chelating agent such as deferoxamine (DFO), bathocuproinedisulfonic acid (BCDS). BT induced DNA damage in dose-dependent manner at concentration between 10$\mu\textrm{m}$ and 100$\mu\textrm{m}$. The antioxidant vitamin C itself induced DNA damage at higher concentration. The DNA damage induced by BT in HL-60 cells was protected at low concentraiton of vitamin C whereas no protective effect was found at high concentration. In hibitory effect of SOD on DNA damage by BT was observed and this suggested that BT produce superoxide anion (O2-) causing DNA damage. Catalase protected BT-induced DNA damage suggesting that BT produce H2O2 during autooxidation of BT. Both Fe(II)-specific cheiating agent, deferoxamine (DFO) and Cu(I)-specific chelating agent, bathocuproinedisulfonic acid (BCDS) inhibited BT0induced DNA damage. This suggested that DNA damage was caused by active species which was produced DAN damage. This suggested that DNA damage was caused by active species which was produced by the autooxidation of BT in the presence of Cu(II) and Fe(III). These findings suggest that reactive oxygen species play an important role in the mechanism of toxicity induced by benzene metabolites.

Onion Supplementation Inhibits Lipid Peroxidation and Leukocyte DNA Damage due to Oxidative Stress in High Fat-cholesterol Fed Male Rats

  • Park, Jae-Hee;Seo, Bo-Young;Lee, Kyung-Hea;Park, Eun-Ju
    • Food Science and Biotechnology
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    • v.18 no.1
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    • pp.179-184
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    • 2009
  • The aim of this study was to investigate effects of onion, red onion, or quercetin on plasma antioxidant vitamin, lipid peroxidation, and leukocyte DNA damage in rats fed a high fat-cholesterol diet. Forty SD male rats were assigned to normal control, high fat-cholesterol diet (HF), or HF+5% onion powder, HF+5% red onion powder, or HF+0.0l% quercetin. The HF diet resulted in significantly higher plasma lipid peroxidation which decreased with onion, red onion, or quercetin supplementation. Leukocyte DNA damage induced by HF diet decreased significantly in rats fed onion and red onion, while quercetin supplementation had no effect on preventing leukocyte DNA damage. $H_2O_2$ induced leukocyte DNA damage exhibited a highly significant negative correlation with plasma retinol and tocopherols. These results suggest that onion or red onion powder exerts a protective effect with regard to DNA damage in rats fed HF diet. However, 0.01% quercetin in pure form might not be effective at preventing DNA damage.

Single Cell Gel Electrophoresis (comet assay) to Detect DNA Damage and Apoptosis in Cell Level (DNA damage와 Apoptosis를 정량화하는 단세포전기영동법)

  • 류재천;김현주;서영록;김경란
    • Environmental Mutagens and Carcinogens
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    • v.17 no.2
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    • pp.71-77
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    • 1997
  • The single cell gel electrophoressis(SCGE) assay, also known as the comet assay, is a rapid, simple, visual and sensitive technique for measuring and analysing DNA breakage in mammalian cells. The SCGE or comet assay is a promising test for the detection of DNA damage and repair in individnal cells. It has widespread potential applications in DNA damage and repair studies, genotoxicity testing and biomonitoring. In this microgel electrophoresis technique, cells are embedded in agarose gel on microscope slides, iysed and electrophoresed under alkaline conditions. Cells with increased DNA damage display increased migration of DNA from the nucleus towards the anode. The length of DNA migration indicates the amount of DNA breakage in the cell. The comet assay is also capable of identifying apoptotic cells which contain highly fragmented DNA. Here we review the development of the SCGE assay, existing protocols for the detection and analysis of comets, the relevant underlying principles determining the behaviour of DNA and the potential applications of the technique.

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Use of comet assay as a bioassay in marine organisms exposed to genotoxicants (유전독성물질로 오염된 해양생물의 생물검정법으로서 comet assay 이용)

  • Kim Gi-Beum;An Joon-Gun;Kim Jae-Won
    • Journal of Environmental Science International
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    • v.14 no.11
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    • pp.1071-1079
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    • 2005
  • Using single cell gel electrophoresis, DNA single strand breaks were determined in various marine organisms. DNA damage on fish blood cells was detected to know whether there was a difference between Incheon, Pohang, Masan, and Tongyeong as a control site. Tongyeong showed the lowest DNA damage among the study areas. Mussels, transplanted to Masan Bay for one month, revealed high DNA damage at sites with high economical activity. In two weeks exposure of polychaete to Incheon sediments, higher DNA damage was detected in the sediment adjacent to Incheon harbor than open sea. These results suggested that the marine organism from the polluted area revealed a relatively high DNA damage. In addition, these areas might be contaminated with genotoxic compounds and comet assay was useful as a bioassay to detect DNA damage in marine organisms.

Phenanthrene-induced Oxidative DNA Damage of Lymphocytes and the Suppression by Ginseng Extract (페난트렌에 의한 임파구 DNA의 산화적 손상과 인삼추출물에 의한 억제)

  • Yoo, Ah-Reum;Lee, Mi-Young
    • Journal of Ginseng Research
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    • v.33 no.4
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    • pp.355-360
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    • 2009
  • Phenanthrene ($C_{14}H_{10}$) is a polycyclic aromatic hydrocarbon with three aromatic rings, and it can be produced by incomplete combustion of fossil fuels. Comet assay was used to examine the oxidative DNA damage of lymphocytes by phenanthrene and to measure the suppressive effects of ginseng extract on the DNA damage in this investigation. The in vitro oxidative DNA damage by phenanthrene increased in a dose-dependent manner in the lymphocyte. However, the DNA damage was significantly inhibited by ascorbate. Moreover, pretreatment, cotreatment and posttreatment with ginseng extract enhanced lymphocyte resistance to the phenanthrene-induced DNA damage. Phenanthrene enhanced the generation of intracellular reactive oxygen species, and the elevated reactive oxygen species level was reduced by treatment with ginseng extract.

Radiation Protective Effect of vitamin C and Cysteine on DNA Damage in Mice Splenic Lymphocytes by Single Cell Gel Electrophoresis Assay (단세포 겔 전기영동법을 이용한 생쥐 비장 림프구 DNA 손상에 대한 비타민 C 및 시스테인의 방사선 방어효과)

  • 천기정;김진규;김봉희
    • Environmental Analysis Health and Toxicology
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    • v.16 no.1
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    • pp.17-20
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    • 2001
  • The alkaline comet assay, employing a single-cell gel electrophoresis(SCGE), is a rapid, simple and sensitive technique for visualizing and measuring DNA damage leading to strand breakage in individual mammalian cells. The protecting effect of pretreatment with vitamin C and cysteine on the DNA damage of gamma ray was investigated in mice splenic lymphocytes. Vitamin C and cysteine were administered orally for five consecutive days before irradiation. Four week old ICR male mice were irradiated wish 3.5Gy of γ-radiation and were sacrificed 3 days later. Spleens were taken for DNA damage examination by Comet assay and the tail moments of DNA single -strand breaks in tole splenic lymphocytes were evaluated. The results show that pretreatment with vitamin C and cysteine were effective in protecting against DNA damage by gamma ray. Administration of antioxidants like vitamin C and cysteine to mice before irradiation was effective in reducing the tail moment of splenic lymphocytes DNA.

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DNA Damage Protection and Anti-inflammatory Activity of Different Solvent Fractions from Aruncus dioicus var. kamtschaticus

  • Zhang, Qin;Kim, Hye-Young
    • Korean Journal of Plant Resources
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    • v.27 no.6
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    • pp.714-719
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    • 2014
  • This study investigated DNA damage protection and anti-inflammatory activity of different solvent fractions from Aruncus dioicus var. kamtschaticus (A. dioicus) aerial parts water extract. As for DNA damage protection, distilled water ($H_2O$) fraction displayed the most powerful protection for DNA damage at a concentration of 1 mg/ml. As for anti-inflammatory activity, dichloromethane ($CH_2Cl_2$) fraction exhibited the highest NO inhibition activity, ranging from 61% to 19% ($10-40{\mu}g/ml$). Furthermore, the levels of pro-inflammatory cytokines mRNA expressions and intracellular reactive oxygen species (ROS) were employed to verify the anti-inflammatory activity of the $CH_2Cl_2$ fraction on further researches. It could be concluded that A. dioicus had a significantly effect of DNA damage protection and anti-inflammatory activity which also as an essential edible vegetable and medicinal species.