• Title/Summary/Keyword: 소핵

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Galangin의 유전독성 억제효과에 관한 연구

  • 허문영;윤여표
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.325-325
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    • 1994
  • 본 연구에서는 먼저 14종의 flavonoid화합물을 대상으로 발암물질로서 잘 알려져있는 benzo(a)pyrene[B(a)P]에 대한 소핵생성억제효과를 관찰하였다. 소핵시험을 이용한 유전독성억제실험에서 비적적 큰 활성을 보이는 flavonoid는 2,3 이중결합과 3,5,7-trihydroxyl기를 갖는 polyhydroxy flavonol화합물들이었다. 이중에서 galangin은 활성이 비교적 컸으며, 이같은 유전독성억제효과는 galangin투여시 B(a)P의 대사활성화가 감소되고 활성본태산물들의 DNA binding을 저해함으로서 나타났다. 한편, galangin은 대사활성화가 필요없는 1차 발암물질인 N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)에 의한 소핵생성도 감소시켰다. 이러한 galangin의 alkylating agent에 대한 유전독성억제효과는 calf thymus DNA를 이용한 실험에서 DNA의 메칠화를 저해하는 기전으로 나타나는 것으로 판단되었다. galangin은 mitouycin과 같은 DNA cross-linking agent에 의한 소핵생성에도 억제효과를 나타내었다. 특히 동시투여(simultaneous treatment)나 사후투여(post-treatment)시보다 사전투여(pre-treatment)시에 소핵생성억제효과가 컸으며 사전연속투여(multiple Pre-treatment)시에는 낮은 용량에서도 효과가 컸다. 이러한 저용량의 사전연용투여에 의한 유전독성억제효과들은 B(a)P나 MNNG에 대해서도 잘 나타났다.

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Evaluation of the Genetic Toxicity of Synthetic Chemicals(XIV) -In vivo Bone Marrow Micronucleus Assay of 11 Synthetic Chemicals in Mice- (합성화학물질들의 유전독성평가(XIV)-마우스의 골수세포를 이용한 11종 합성화학물질들의 생체내 소핵시험-)

  • Ryu Jae Chun;Kim Youn Jung
    • Environmental Analysis Health and Toxicology
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    • v.19 no.3
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    • pp.307-314
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    • 2004
  • 합성화학물질들이 환경으로의 유입은 인체에는 물론 환경생태계에 많은 영향을 미치므로 이들의 유해성 검증은 매우 중요한 일이라 할 수 있다. 실제 산업체에서 사용되는 수많은 화학물질들의 유전적 손상 유발유무는 유해성검증에서 무엇보다 중요한 일이라 할 수 있다. 이에 산업체 공정과정에서 널리 사용되는 것으로 알려진 11종의 합성화학물질에 대해 마우스의 골수 세포를 이용한 in vivo소핵시험을 수행하여, 소핵형성 유발유무를 관찰하였다. 양성대조군으로 사용된 mitomycin C는 음성대조군과 비교시 유의하게 소핵을 유발하는 반면, 비교적 마우스에서 높은 50%치사량을 보이는 thiourea, 2,4-dichlorophenol 및 2,4-toluene diisocyanate 등의 합성물질들을 비롯한 나머지 8종의 물질들은 본 실험결과 통계적으로 유의하게 소핵을 유발하지 않는 것을 관찰 할 수 있었다.

Analysis of radiation-induced micronuclei and aneuploidy involving chromosome 1 and 4 by FISH technique (FISH 기법을 이용한 방사선에 의한 소핵과 이수성 분석)

  • Chung, Hai-Won;Kim, Tae-Yon;Cho, Yoon-Hee;Kim, Su-Young;Kang, Chang-Mo;Ha, Sung-Whan
    • Journal of Radiation Protection and Research
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    • v.29 no.4
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    • pp.243-249
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    • 2004
  • The cytokinesis-block micronucleus (CBMN) assay in combination with FISH technique using chromosome-specific centromeric probes for chromosome 1 and 4 was performed in mitogen stimulated human lymphocytes which were exposed to x-radiation to identify different sensitivity of chromosomes to the induction of micronuclei(MN) and aneuploidy by radiation. The frequencies of micronucleated cytokinesis-blocked(MNCB) cells and MN in binucleated lymphocytes(BN) increased with the increase in radiation dose. A significant induction of aneuploidy of chromosome 1 and 4 were found. The frequency of aneuploidy of chromosome 1 and 4 in the control were 9 per 2,000 BN cells and this increased to 47 and 71 following irradiation at a dose of 1 and 2 Gy, respectively. The induction of aneuploidy of chromosome 1 was higher than that of chromosome 4. The frequency of aneuploid BN cells with MN exhibiting positive centromere signal for either chromosome 1 and/or 4 increased in a dose dependent manner, and that for chromosome 1 is higher than that for chromosome 4. Among the total induced MN in irradiated lymphocytes, smaller proportion of MN exhibit centromeric signal of chromosome indicating that radiation-induced MN are mainly originated from chromosomal breakage rather than chromosomal non-disjunction. These results suggest that x-radiation can induce aneuploidy and supports the finding that chromosome vary in their sensitivity to aneuploidy induction by x-irradiation.

Effect of Cytosine Arabinoside, 3-Aminobenzamide and Hydroxyurea on the frequencies of radiation-induced micronuclei and aneuploidy in human lymphocytes (DNA 회복 저해제 Cytosine Arabinoside, 3-Aminobenzamide 및 Hydroxyurea가 방사선에 의해 유도된 소핵과 이수성에 미치는 영향)

  • Cho, Yoon-Hee;Kim, Yang-Jee;Kang, Chang-Mo;Ha, Sung-Whan;Chung, Hai-Won
    • Journal of Radiation Protection and Research
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    • v.30 no.4
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    • pp.209-219
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    • 2005
  • This study was carried out to examine the effect of the DNA repair inhibitors, Cytosine Arabinoside(Ara C), 3-Aminobenzamide(3AB) and Hydroxyurea(HU) on the frequencies of radiation-induced micronuclei(MNi) and aneuploidy. Irradiated lymphocytes(1-3Gy) were treated with DNA repair inhibitors, Ara C, 3AB and HU for 3 hours and CBMN assay - FISH technique with DNA probe for chromosome 1 and 4 was performed. The frequencies of x-ray induced MNi and aneuploidy of chromosome 1 and 4 were increased in a dose-dependent manner. Ara C, 3AB and HU enhanced the frequencies of radiation-induced MNi and the frequencies of radiation-induced aneuploidy of chromosome 1 and 4 were enhanced by HU and Ara C while no effect was observed by 3AB. The frequency of radiation-induced aneuploidy of chromosome 1 was higher than that of chromosome 4. These results suggest that there are different mechanisms involved in the formation of MNi and aneuploidy by radiation.

Evaluation of the Genetic Toxicity of Synthetic Chemicals (XV) -In vivo Peripheral Blood Reticulocytes Micronucleus Assay of 17 Synthetic Chemicals in Mice- (합성화학물질들의 유전독성평가(XV) -마우스의 말초혈의 망상적혈구를 이용한 17종 합성화학물질들의 생체내 소핵시험-)

  • Kim Mi-Soon;Kim Youn-Jung;Ryu Jae-Chun
    • Environmental Analysis Health and Toxicology
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    • v.21 no.3 s.54
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    • pp.209-218
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    • 2006
  • 합성화학물질들이 환경으로의 유입은 인체에는 물론 환경생태계에 많은 영향을 미치므로 이들의 유해성 검증은 매우 중요한 일이라 할 수 있다. 실제 산업체에서 사용되는 수많은 화학물질들의 유전적 손상 유발유무는 유해성검증에서 무엇보다 중요한 일이라 할 수 있다. 이에 산업체 공정과정에서 널리 사용되는 것으로 알려진 17종의 합성화학물질에 대해 마우스의 말초 혈의 망상적혈구를 이용한 in vivo 소핵시험을 수행하여, 소핵형성 유발유무를 관찰하였다. 양성대조군으로 사용된 mitomycin C는 음성대조군과 비교시 유의하게 소핵을 유발하는 반면, 비교적 마우스에서 높은 50% 치사량을 보이는 benzoyl chloride, p-toluene sulfonic acid 및 4,4'-sulfonyldianiline 등의 합성물질들을 포함한 총 17종의 물질들은 본 실험결과 통계적으로 유의하게 소핵을 유발하지 않는 것을 관찰 할 수 있었다.

Galangin의 MNNG 또는 Bleomycin유도 염색체 손상에 대한 억제효과

  • 허문영;윤여표;이병무
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1993.04a
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    • pp.99-99
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    • 1993
  • 본 연구에서는 이미 benzo(a)pyrene유도 소핵시험에서 뚜렷하게 소핵생성억제능을 보인 polyhydroxy flavonol유도체중의 하나인 Galangin에 대하여 C57BL/6 mice를 이용하여 N-methyl-N'-nitro-N-nitrosoguanidine(이하 MNNG)에 의해 유도된 소핵생성빈도에 미치는 영향을 살펴보고, spleen lymphocyte 배양을 통해 bleomycin 및 MNNG유도 염색체이상에 미치는 영향과 MNNG에 의해 유발된 DNA adduts중 biomarker로서 7-methylguanine형성에 대한 Galangin의 영향을 살펴봄으로서 ,Galangin의 유전독성 억제효과 및 작용기전에 대한 연구를 하고자하며 향후 Galangin을 모핵으로하는 cancer chemopreventive agent로의 유도체 합성에 기여하고자 한다.

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The Micronucleus Test of the Diglyceride Preparation with Conjugated Linoleic Acid by Using Mice (마우스를 이용한 공액리놀레산 함유 디글리세라이드 조성물에 대한 소핵시험)

  • Hong, Soon-Gi;Chung, Shin-Gyo;Hyun, Sun-Hee
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.37 no.7
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    • pp.853-857
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    • 2008
  • To assess the clastogenic effects of the diglyceride preparation containing conjugated linoleic acid (DG+CLA) in vivo micronucleus test was performed using ICR mice. Each of the groups consisted of three doses of DG+CLA (500, 1,000 and 2,000 mg/kg, p.o.), Mitomycin C (positive control, 2 mg/kg, i.p.) and negative control (olive oil, 10 mL/kg, p.o.). A slide preparation was made at 24 hours after 1st treatment with DG+CLA. As a result of counting the icronucleated polychromatic erythrocyte (MNPCE) of 2,000 polychromatic erythrocyte (PCE), the number of aberrant cells was not increased in any of the three doses of DG+CLA orally administered. There was no clinical sign connected with administration of DG+CLA. These results indicate that DG+CLA is not capable of inducing micronuclei in vivo mice cells and thus has no genotoxicity in micronucleus.

Evaluation of the Genetic Toxicity of Synthetic Chemicals (Ⅷ) - In vivo Bone Marrow Micronucleus Assay of 8 Synthetic Chemicals in Mice - (합성화학물질들의 유전독성평가(Ⅷ) -마우스의 골수세포를 이용한 8종 합성화학물질들의 생체내 소핵시험-)

  • Ryu, Jae-Chun;Kim, Kyung-Ran;Kim, Youn-Jung
    • Environmental Analysis Health and Toxicology
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    • v.18 no.2
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    • pp.137-143
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    • 2003
  • To validate and to estimate the chemical hazard playa very important role to environment and human health. The detection of many synthetic chemicals used in industry that may pose a genetic hazard in our environment is of great concern at present. Since these substances are not limited to the original products, and enter the environment, they have become widespread environmental pollutants, thus leading to a variety of chemicals that possibly threaten the public health. In this resepct, the clastogenicity of 8 synthetic chemicals was evaluated with bone marrow micronucleus assay in mice. The positive control, mitomycin C(2mg/kg,i.p.) revealed significant induction ratio of percentage of micronucleated polychromatic erythrocytes/l,000 polychromatic erythrocytes compared to carboxymethylcellulose control. The chemicals with relatively high LD$\_$50/ value such as phenylisocyanate (CAS No. 103-71-9), m-aminochlorobenzene (CAS No. 108-42-9) and 2-chloro-4-nitroaniline (CAS No. 121-87-9) revealed no significant induction of micronucleated polychromatic erythrocytes in mice. From this results, 8 synthetic chemicals widely used in industry have revealed no significant micronucleus induction of clastogenicity in mice in this experiment.

Micronucleus Test of Wild Ginseng Culture Extract Using the Marrow Cells in ICR Mice (산삼배양추출물의 ICR 마우스 골수세포를 이용한 복강 투여 소핵시험)

  • Song Si-Whan;Yang Deok Chun;Choung Se Young
    • Journal of Food Hygiene and Safety
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    • v.20 no.1
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    • pp.58-63
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    • 2005
  • To assess clastogenic effects of the wild ginseng culture extract (WGCE) in vivo micronucleus test was performed using 7 weeks old ICR mice. At 24 hours after 2nd treatment with wild ginseng culture extract at the doses of 0, 500, 1,000, and 2,000 mg/kg/day by peritoneal route mice were sacrified and marrow cells were prepared for smear slides. As a result of counting the micronucleated polychromatic erythrocyte (MNPCE) of 2,000 polychromatic erythrocyte(PCE), all treatment groups did not show statistically significant increase than negative control group. And there was no clinical sign connected with injection of wild ginseng culture extract. It was concluded that wild ginseng culture extract did not induce micronucleus in the marrow cells of ICR mice.

In vivo Micronucleus Test of Cyclohexanone and Mutagenicity Classification According to a Globally Harmonized System (Cyclohexanone의 in vivo 소핵시험을 통한 GHS 변이원성 구분)

  • Kim, Soo-Jin;Rim, Kyung-Taek;Lim, Cheol-Hong
    • Journal of Life Science
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    • v.24 no.7
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    • pp.804-811
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    • 2014
  • A micronucleus test of cyclohexanone has not yet been conducted. To classify the chemical hazard posed by cyclohexanone according to a globally harmonized system of classification and labeling of chemicals (GHS), we investigated its mutagenicity by micronucleus induction in ICR bone marrow cells of 7-weeek-old male mice. The mice were administered three dosages of the chemical for 24 hr via the oral route. After 24 hr, the mice were sacrificed, and their bone marrow cells were prepared for smearing slides. Based on counts of micronucleated polychromatic erythrocytes (MNPCEs) of 2,000 polychromatic erythrocytes, cyclohexanone did not inhibit bone marrow cell proliferation in any of the treated groups, but it resulted in micronucleus induction. According to the results of the mammalian bone marrow micronucleus test, this chemical is mutagenic and classified as category 2 in the GHS.