• Title/Summary/Keyword: Human DNA

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Molecular and Genomic Approaches on Nickel Toxicity and Carcinogenicity

  • Seo, Young-Rok;Kim, Byung-Joo;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.1 no.2
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    • pp.73-77
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    • 2005
  • Nickel is the one of potent environmental, the occupational pollutants and the classified human carcinogens. It is a serious hazard to human health, when the metal exposure. To prevent human diseases from the heavy metals, it is seemingly important that understanding of how nickel exerts their toxicity and carcinogenic effect at a molecular and a genomic level. The process of nickel absorption has been demonstrated as phagocytosis, iron channel and diffusion. Uptaked nickel has been suggested to induce carcinogenesis via two pathways, a direct DNA damaging pathway and an indirect DNA damaging pathway. The former was originated from the ability of metal to generate Reactive Oxygen Species (ROS) and the reactive intermediates to interact with DNA directly. Ni-generated ROS or Nickel itself, interacts with DNAs and histones to cause DNA damage and chromosomal abnormality. The latter was originated from an indirect DNA damage via inhibition of DNA repair, or condensation and methylation of DNA. Cells have ability to protect from the genotoxic stresses by changing gene expression. Microarray analysis of the cells treated with nickel or nickel compounds, show the specific altered gene expression profile. For example, HIF-I (Hypoxia-Inducible Factor I) and p53 were well known as transcription factors, which are upregulated in response to stress and activated by both soluble and insoluble nickel compounds. The induction of these important transcription factors exert potent selective pressure and leading to cell transformation. Genes of metallothionein and family of heat shock proteins which have been known to play role in protection and damage control, were also induced by nickel treatment. These gene expressions may give us a clue to understand of the carcinogenesis mechanism of nickel. Further discussions on molecular and genomic, are need in order to understand the specific mechanism of nickel toxicity and carcinogenicity.

Binding Mode Studies of Indenoisoquinoline Analogues into Human Topoisomerase I-DNA Complex Using Flexible Docking (Human Topoisomerase I-DNA 절개가능 복합체에 대한 Indenoisoquinoline 유도체들의 결합양상 연구)

  • Park, In-Seon;Kim, Bo-Yeon;Kim, Choon-Mi;Choi, Sun
    • YAKHAK HOEJI
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    • v.53 no.4
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    • pp.228-234
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    • 2009
  • Topoisomerase I (Topo I) participates in the DNA replication, transcription, and repair. Binding of Topo I inhibitor to the Topo I-DNA cleavage complex forms stabilized ternary complex which blocks DNA religation and ultimately causes cell death. Camptothecin (CPT) and its derivatives have been among the most effective anticancer drugs by inhibition of topo I. However, efforts to synthesize non-CPT drugs have been actively going on because the CPT derivatives have several limitations such as poor solubility, short half-life, and side effects. As an indenoisoquinoline, NSC314622 is not as potent as CPT, but its chemical stability and slower reversibility of the cleavage complex made it a good lead compound. Recently, a series of indenoisoquinoline analogues were synthesized with substituted dimethoxy or methylenedioxy on the aromatic ring and alkylamino on the lactam nitrogen. Some of them showed quite good Topo I inhibitory activity. Using the computer docking program, Surflex-Dock, indenoisoquinoline analogues were docked into the human Topo I-DNA cleavable complex. The docking results showed that the compounds with activity better than NSC314622 intercalated between the -1 and +1 base pairs at the cleavage site, but those with little or no activities did not appear to intercalate. These results could be useful to design new Topo I inhibitors improved than CPT.

The genetic analysis on ancient human bone in jar coffin excavated from Naju Bokam-ni 3rd tumulus (출토 인골의 유전자분석-나주 복암리 3호분 옹관 인골을 중심으로)

  • Lee, Kyu-Sik;Chung, Yong-Jae;Han, Sung-Hee;Lee, Myong-Hee;Han, Myun-Soo;Choi, Dong-Ho
    • 보존과학연구
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    • s.20
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    • pp.5-20
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    • 1999
  • We have analyzed the allele and genotype frequencies from 10 fractions of ancient human skeleton in 3 pieces of Jar coffin excavated from Naju Bokamni3rd tumulus by PCR amplification, high resolution polyacrylamide gelelectorphoresis and silver staining. We could isolate human genomic DNA from 3 bone fractions but the rest of them could not be used as materials due to being decayed. We could detect sex determination as male and 3 genotypes of STR system, HUMTHO1, HUMTPOX and HUMC5F1PO from the bone fraction of left side in Jar coffin 3 and see the slightly reaction suggesting the sex as male from the bone fraction of the left side in Jar coffin 2 and female from the right side in Jar coffin 3.We have also analyzed the genotype frequencies of mitochondria from the bone fractions of the left side and the right side in jar coffin 3, respectively. From the result of indetifiying at nucletide position between 16018 and 16378of the base of hyper variable region(HV1) in the control region, We can presume that the both bones have the same maternal inheritance.

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Evaluation of the preservation state of human skeletal remains using real-time PCR (출토 인골 DNA의 real-time PCR 정량에 의한 보존상태 평가 연구 - 부여 오수리 출토 인골을 중심으로 -)

  • Kwon, Eun-Sil;Cho, Eun-Min;Kim, Sue-Hoon;Kang, Soyeong
    • 보존과학연구
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    • s.32
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    • pp.171-183
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    • 2011
  • In this study molecular genetic analysis was carried out on 4 human skeletal remains from Osuri, Buyeo. We showed that real-time PCR is the method of the choice to assess the initial number of genuine ancient DNA molecules. Human mitochondrial DNA quantification was accomplished by the real-time PCR for the cytochrome b gene of the mitochondria. Histological results proved to be a good potentiality for biochemical analysis using biomolecule. The level of specimen's preservation state was proved that level of quantitative result was BO-04, BO-01, BO-03, BO-02. Continually, we showed that biochemical and biomolecule results for the level of preservation state were similar. This study will be useful to important material for predicting biochemistry and biology analysis of the ancient bone.

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Effects of Storage Buffer and Temperature on the Integrity of Human DNA

  • Kim, Yun-Tae;Choi, Eun-Hee;Son, Bo-Kyoung;Seo, Eun-Hee;Lee, Eun-Kyoung;Ryu, Je-Kwon;Ha, Gi-Won;Kim, Jin-Seon;Kwon, Mi-Ran;Nam, Jae-Hoon;Kim, Young-Jin;Lee, Kyoung-Ryul
    • Korean Journal of Clinical Laboratory Science
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    • v.44 no.1
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    • pp.24-30
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    • 2012
  • In this study, we have examined the effects of the storage time and temperature on DNA quality and have also studied the effects of the hydration buffer in which DNA is dissolved. This study was performed using 160 human blood samples collected with informed consent from 2007 to 2008 in the hospital where this cohort study was performed. The DNA extracted was dissolved using distilled water (DW) or Tris-EDTA (TE) buffer, and stored in the deep freezer or refrigerator for up to 10 weeks at $-70^{\circ}C$, $-20^{\circ}C$, $4^{\circ}C$, and $25^{\circ}C$, respectively. DNA integrity was determined by the degree of smearing of DNA on the gel. After four weeks, all of the 20 DNA samples dissolved in DW and stored at $25^{\circ}C$ were entirely degraded. After 10 weeks, 6 of the 20 DNA samples dissolved in TE buffer and stored at $25^{\circ}C$ were fairly degraded, and 4 of the 20 DNA samples dissolved in DW and stored at $4^{\circ}C$ were fairly degraded. The 20 DNA samples dissolved in TE buffer and stored at $4^{\circ}C$ were stable for 10 weeks. DNA samples stored at $-20^{\circ}C$ and $-70^{\circ}C$ did not appear to degrade in either DW or TE buffer, even at the 10-week point. We suggest that TE buffer should use for DNA elution, in order to protect against degradation and to preserve DNA for a long period of time, and the samples should be stored at $-20^{\circ}C$ or $-70^{\circ}C$.

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Synergistic antitumor activity of ST1571 and camptothecin in human cancer cells (Camptothecin 에 의한 ST1571 의 항암 활성 증강)

  • Kim, Mi-Ju;Lee, Sang-Min;Bae, Jae-Ho;Chung, Byung-Seon;Kang, Chi-Dug;Kim, Sun-Hee
    • Journal of Life Science
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    • v.17 no.6 s.86
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    • pp.748-755
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    • 2007
  • The in vitro activity of ST1571, an inhibitor of the Abl group of protein-tyrosine kinases, alone or in combination with camptothecin (CPT), a specific topoisomerase I inhibitor, was evaluated against human cancer cells with different metastatic capacity and drug resistance potency. These cell lines showed different sensitivity to ST157 on growth inhibition, and the expression of DNA-dependent protein kinase (DNA-PK), which interacts constitutively with c-Abl, was significantly decreased in drug sensitive CEM and MCF-7 cells and poorly metastatic PC3 and KMl2 cells as compared with that of multidrug resistant CEM/MDR and MCF-7/MDR cells and highly metastatic PC3-MM2 and KM/L4a cells, respectively. These results suggest differential modulation of DNA-PK by ST1571 treatment in drug resistance and metastatic degree dependent manner. We showed that CPT as well as ST1571 significantly inhibits the expression of DNA-PK. The combined treatment with ST15fl and CPT revealed synergistic effect, and the effect was accompanied by inhibition of cell proliferation due to significant reduced expression of DNA-PK components, which resulted in CPT sensitizes human cancer cells resistant to ST1571. Therefore, the results of our study suggested that the suppression of DNA-PK using combination of ST1571 and CPT could be a novel molecular target for against drugresistant and metastatic cancer cells.

A Study on Sijo Literature Therapy structuralized in the Rated Codon

  • Park, In-Kwa
    • International Journal of Advanced Culture Technology
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    • v.5 no.2
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    • pp.9-18
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    • 2017
  • The purpose of this study is to find out how to use emotional activity rate in sentence. The aim is to estimate the Emotion-Codon status of emotion-DNA wiggling as well as the sequence of codons in which amino acids of human body are spread. It is as if the amino acids are translated from the DNA of the human body, and the emotions that cooperate with each other are diversified and refined. Through these attempts, we anticipate the change of emotions by literary works and present the direction of the synapse working and the direction of the encoding. Therefore, this study analyzed the emotional activity of Rated Emotion-Codon, which works as Rated Sijo. At this time, the emotional change in the human body, in which the sentence is more clearly pronounced, is predicted and detected. This result shows how emotions can activate the human body. This state of activation is an indicator of how much the sentence pushes the physiological action of the human body. It is judged that Codon is constructed precisely for the activation of the rated Sijo additive definition by this index. Our result is evidenced by the fact that three sentences of Rated Sijo show an array with the same rating as the Rated Codon's, The first sentence fuses with the sentiment between the second sentence and the third sentence of Rated Sijo. The emotional symbols between the sentence symbols "A, U, J, L" in the first base of the Codon table and the sentences fusing between the sentences of the first sentence and the third sentence are "A, U, J, L". The emotional symbols between the sentences flowing in the second base of the Codon table and between the sentences of the first sentence and the second sentence are structured in the third base of the Codon table as "A, U, J, L". The Rated Sijo, which is resiliently and precisely assigned to the human body's Rated Emotion-Codon, will require a rich experience in our Rated Life.

Analysis of chromosome aberration, sister chromatid exchange, micronuclei and single cell gel electrophoresis in human lymphocytes exposed in vitro to Bisphenol A and Diethylstilbestrol (비스페놀 A 및 Diethylstilbestrol의 유전독성 평가를 위한 염색체이상, 자매염색분체교환, 소핵형성, 단일세포 겔 전기영동법의 활용)

  • 김병모;정해원
    • Environmental Mutagens and Carcinogens
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    • v.21 no.2
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    • pp.135-141
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    • 2001
  • Endocrine disruptors have been implicated in carcinogenesis in animal studies, but carcinogenetic effects on human remain controversial. In order to examine the genotoxicity of two common endocrine disruptors, Bisphenol A and Diethylstilbestrol, cytogenetic endpoints including chromosome aberration (CA), sister chromatid exchange (SCE), micronuclei (MN) analyses and DNA damage by single cell gel electrophoresis (SCGE) were assessed. The effects of Bisphenol A and Diethylstilbestrol on the frequencies of CA and MN were increased in a dose-dependent manner and that of Bispheol A was more significant by Kendall'$\tau$test. Bisphenol A and Diethylstilbestrol also increased the frequency of SCE. Bisphenol A and Diethylstilbestrol induced DNA damage in a dose-dependent manner and the DNA damage induced by Diethylstilbestrol in human blood lymphocytes was more significant.

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Genomic and Proteomic Profiling of the Cadmium Cytotoxic Response in Human Lung Epithelial Cells

  • Choi, Kwang-Man;Youn, Hyung-Sun;Lee, Mi-Young
    • Molecular & Cellular Toxicology
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    • v.5 no.3
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    • pp.198-206
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    • 2009
  • Microarray and proteomic expression patterns in response to cadmium exposure were analyzed in human lung epithelial cells. Among 35,000 genes analyzed by cDNA microarray, 228 genes were up-regulated and 99 genes were down-regulated, based on a fold change cut-off value of ${\geq}2$. Combining two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight-mass spectrometry (MALDI-ToF-MS), 25 of 629 protein spots showed fold changes in expression ${\geq}2$ (17 up-regulated, 8 down-regulated). After comparing the cDNA microarray and proteomic analyses, only transglutaminase 2, translation elongation factor 1 alpha 1, and glyceraldehyde-3-phosphate dehydrogenase showed overlapping signals in the cDNA microarray and proteomic analyses, whereas the remaining differentially expressed proteins showed large discrepancies with respect to mRNA expression.

DETECTION OF HUMAN PAPILLOMAVIRUS DNA IN RESPIRATORY TRACT PAPILLOMA USING POLYMERASE CHAIN REACTION(PCR) (중합효소 반응을 이용한 후두유두종 Human papillomavirus DNA의 검색)

  • 김광현;성명훈;정원호;최영민;박경찬
    • Proceedings of the KOR-BRONCHOESO Conference
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    • 1991.06a
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    • pp.18-18
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    • 1991
  • 후두유두종은 호흡기계에 발생하는 양성종양중 가장 흔한 질환으로 연령에 따라 소아형과 성인형으로 분류하는데 다발성 병변이 흔하고 재발율이 높다고 알려져 있다. 후두유두종의 원인으로는 human papillomavirus의 감염으로 생각되며 잠복 감염으로 인하여 후두유두종이 재발된다고 알려져 있다. Gissman등에 의해 HPV 11이 발견되었음이 보고된 이래 최근까지 HPV 6와 11이 후두유두종의 원인이 된다고 알려져 있다. HPV의 검출에는 Southern blotting이나 in-situ hybridization 방법이 알려져 있는데 저자들은 현재까지의 바이러스 검색방법 중 가장 예민한 방법인 PCR을 이용하여 후두유두종의 HPV DNA를 조사하여 보고자 한다. 저자들은 1989년 10월부터 1900년 12월까지 서울대병원 이비인후과에서 수술을 시행받은 후두유두종 환자 15예를 대상으로 하였으며 이중 소아형은 9예이었고 성인형은 6예였으며 대부분 다발성 병변이었다. HPV 6는 15예중 10예에서 HPV 11은 15예중 6예에서 발견되었으며 두가지 형이 같이 발견된 경우는 1예가 있었다. 소아형의 경우에는 HPV 6와 11이 각각 5예로 비슷한 비율로 검출된 반면 성인형에서는 HPV 6가 주로 검출되었다.

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