• Title/Summary/Keyword: 유전자독성

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Influences of CYP2E1 Gene Polymorphism on the Metabolism of Benzene (벤젠 대사에 있어서 CYP2E1유전자다형성의 영향)

  • 정효석;김기웅;장성근
    • Toxicological Research
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    • v.18 no.4
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    • pp.325-330
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    • 2002
  • In this study, the biochemical role of genetic polymorphism in modulating urinary excretion of benzene metabolite as phenol level has been investigated in 90 workers exposed to benzene in the petroleum refinery plant of Korea. The mean concentration of volatile benzene in the refinery environment was 0.042 mg/㎥ (SD, 0.069) and that of urinary phenol was 7.42 mg/g creatinine (SD, 11.3). The frequencies of CYP2E1 genotypes, namely CYP2E1$^*1$/$^*1$, CYP2E1$^*1$/$^*2$ and CYP2E1$^*2$/$^*2$ were 2.2% (2 subjects), 6.7% (G subjects) and 91.1% (85 subjects), respectively, and allele frequencies for CYP2E1$^*1$ and CYP2E1$^*2$ were 0.06 and 0.94. The airborne benzene concentration was significantly related to the concentration of phenol in urine (r = 0.640, p < 0.01). The urinary phenol level was significantly correlated with CYP2E1$^*2$/$^*2$ (r = 0.590, p < 0.05). The various biological (i.e. age and liver function parameters) or lifestyle factors (i.e. medication, smoking, alcohol and coffee intake), also taken into account as potential confounders, did not influence the correlation found. These results suggested that CYP2E1 genotypes might play an important role in the metabolism of benzene.

The mRNA Expression of Radio-Sensitive Genes Exposed to Various Dosage of Ionizing Radiation in U-937 Cell (U-937 세포에서 이온화 방사선의 조사선량에 따른 감수성 유전자들의 발현 변화)

  • 김종수;임희영;오연경;김인규;강경선;윤병수
    • Toxicological Research
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    • v.20 no.1
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    • pp.21-29
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    • 2004
  • We used cDNA microarray to assess gene expression profiles in hematopoetic cell line, U-937, exposed to low doses of ionizing irradiation. The 1,000 DNA elements on this array were PCR-amplified cDNAs selected from named human cancer related genes. According to the strength of irradiation, the levels of some gene expression were increased or decreased as dose-dependent manner. The gene expressions of Tubulin alpha, protein kinase, interferon-alpha, -beta, -omega receptor and ras homolog gene family H were significantly increased. Especially, Tubulin gene was shown 2.5 fold up-regulated manner under stress of 500 rad irradiation than 200 rad. On the other hand, fibroblast growth factor 12 and four and a half LIM domains, etc. were significantly down-regu-lated. Also, tumor protein 53(TP53) related genes that p53 inducible protein, tumor protein 53-binding protein looks of little significance as radiation sensitive manner. The radio-sensitivity of tubulin gene etc. that we proposed could be useful to rapid and correct survey for the bio-damage by exposure to low dose irradiation.

Collagen과 osteopontin이 도입된 고기능성 PCL membrane의 제조 및 지방유래 줄기세포의 골세포 분화능 관찰

  • Kim, Yeong-Hui;Song, Ho-Yeon;Jyoti, Anirban;Byeon, In-Seon;Park, Min-Ju;Lee, Byeong-Taek
    • Proceedings of the Materials Research Society of Korea Conference
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    • 2010.05a
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    • pp.42.1-42.1
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    • 2010
  • Poly-carprolactone (PCL)은 생분해성 고분자로 장기간의 임상실험 결과 생체에 독성이 없으며 생체친화성이 우수한 소재로 확인되어 PLGA, PLLA 등과 더불어 조직공학 분야에서 널리 사용되고 있는 생체재료이다. 그러나 PCL은 5개의 비극성 methylene group과 1개의 극성 ester group이 반복되는 지방족의 polyester로 구조상 탄소수가 많아 소수성을 띄는 단점을 가지고 있다. 이러한 표면이 소수성인 재료의 경우, 초기 단백질 흡착능이 떨어져 세포의 부착이 느린 속도로 일어나므로 세포 분화 및 조직 재생이 더디게 일어난다. 본 연구에서는 소수성의 PCL 표면의 단백질 흡착능을 증가시키기 위해 기능성 amine group을 부착하였으며, 또한 골재생을 촉진시킬 수 있는 세포외 기질인 collagen과 osteopontin을 부착함으로써 고기능성 PCL membrane을 제조하였다. 제조된 PCL membrane은 골재생용 조직공학에의 응용을 위해 지방유래 줄기세포를 이용하여 부착능 및 골세포로의 분화능을 확인하였다. 표면 성질의 변화에 의한 세포의 부착능의 변화를 confocal microscopy을 이용하여 부착에 관여하는 단백질의 발현을 확인하였으며, collagen과 osteopontin에 의한 골세포로의 분화능을 확인하기 위해 real time PCR을 통해 골세포의 분화 표지 유전자의 발현을 비교 분석하였다.

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Safety Evaluation on Mutagenicity of White Layer Cake Containing Gamma-Irradiated Egg White (감마선 조사된 난백 함유 White Layer Cake의 돌연변이원성 평가)

  • 김미정;이주운;서지현;송현파;육홍선;최정미;변명우
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.32 no.7
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    • pp.1172-1175
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    • 2003
  • Mutagenicity of white layer cake including 20 kGy-gamma irradiated egg white manufactured as a research on the practical approaches of gamma irradiation for the reduction of egg allergy was evaluated by Salmonella typhimurium reversion assay (Ames test). The water-soluble and organic solvents mixture of methanol: chloroform (2 : 1)-soluble fractions of the white layer cake including 20 kGy-gamma irradiated egg white were examined in S. typhimurium TA98 and TA100. Both with and without metabolic activation, the number of revertant colonies were not increased in each extract compared with negative controls. No significant difference in the formation of the colonies was observed at the non-irradiated and 20 kGy-irradiated samples. The results indicate that there is no evidence of mutagenicity in white layer cake including 20 kGy-gamma irradiated egg white.

Association between CYP1A1 Expression and Childhood Asthma (CYP1A1 유전자발현과 소아천식의 상관)

  • Yang Mihi
    • Environmental Analysis Health and Toxicology
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    • v.20 no.3 s.50
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    • pp.209-213
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    • 2005
  • Due to steady increase of childhood asthma, exposure to air toxics including PAHs have been thought as an etiology for the asthma. PAHs -involvement in airway inflammation, such as IgE production, is the potential mechanism of the PAHs-induced asthma. Cytochrome P450s (CYPs), particularly CYP1A1 is known enzyme to metabolite PAHs and to be induced by PAHs. The CYP1A1 expression has been emphasized as an biomarker for PAHs - exposure. The present study was performed to clarify the etiology of childhood asthma with PAHs-exposure using mRNA expression of CYP1A1 . The study Objects were Korean children who were asthma patients (cases) or other hospital controls (N=20; age,3 $\~$ 16; boys,56$\%$). As result, we detected expression of the CYP1A1 in all peripheral blood specimens which were collected from the subjects. Moreover, we found approx. 300 fold-higher expression of the CYP1A1 in the cases than that in the controls (p(<)0.01). When we considered age which was related to Asthma, the above significant trend was somewhat diluted, however, the relation between asthma and the Cypih i expression waL stronger than that between asthma and age (chi square,7.99 vs. 3.34). Therefore, our study supports that PAHs induce or worse childhood asthma and suggests application of expression of the CYP1A1 as an initiation or progress biomarker for PAHs - induced childhood asthma.

Regulation of CCAAT/enhancer Binding Protein- alpha in Ultraviolet B Responses Involves the Cooperation of p53 and Glycogen Synthase Kinase-3 (자외선 B조사시 p53와 glycogen synthase kinase-3에 의한 CCAAT/enhancer binding protein alpha의 발현조절)

  • Yoon Kyung Sil
    • Environmental Analysis Health and Toxicology
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    • v.20 no.3 s.50
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    • pp.229-235
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    • 2005
  • 태양광선,특히 자외선 B에 대한 환경적 노출은 편평세포암과 기저세포암을 포함하는 흑색선종 이외의 피부암과 크게 관련된다고 알려져 있다. 염기 류신 지퍼계 전사조절인자인 CChAT/enhancer binding protein-alpha는 표피 각질형성세포에서 다량으로 발현되었고, 각질형성세포의 증식을 억제하며 피부암 발생을 억제하는 유전자로서의 역할이 암시된 바 있다. 최근 자외선 B가 각질형성세포에서 p53에 의한 CCAAT/enhanrer binding protein-alpha의 발현을 강력하게 유도한다는 것이 보고되었다. 이러한 CCAAT/enhancer binding protein-alpha 단백질 발현의 유도는 세포 성장 억제 세포고사와 함께 일어났다. 이 연구는 glycogen synthase kinase-3 길항제가 자외선 B에 의한 CCAAT/enhancer binding protein-alpha 유도를 억제하며 변이 kinase-불활성 GSK의 강제 발현은 자외선 B가 CCAAT/enhancer binding protein-alpha전사조절부위 활성의 증가를 억제한다는 것을 보여주었다. 즉 자외선 B에 의한 CCAAT/enhancer binding protein-alpha의 유도가 p53과 활성 glycogen synthase kinase-3에 의한 것이라는 것을 증명하였다.

Expression of Metallothionein mRNA in Cadmium Treated Leydig Cells (테스토스테론생성 레이디히세포(Leydig)에서의 메탈로치오닌 유전자 발현특성연구)

  • Park Kwangsik
    • Environmental Analysis Health and Toxicology
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    • v.19 no.3
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    • pp.261-269
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    • 2004
  • Although the biological functions of metallothioneins (MTs) are still being investigated, they have been suggested to be involved in detoxification of heavy metals, scavenging of free radicals, and protection against alkylating agents. MTs have been reported to be induced in most of animal tissues by heavy metals such as zinc, copper, mercury and cadmium, and the proteins have binding affinities to the metals. However, the presence or induction of MTs was reported not to be clear in leydig cells, which produce testosterone for the maturation of spermatozoa in male testes. In this study, we investigated the inducibility of metallothionein isomers by cadmium in cultured mouse leydig cells. Total RNA was extracted from the near confluent grown leydig cells and RT-PCR was Performed using the Primers which were synthesized on the basis of MT-1, 2, 3 and 4 cDNA from GenBank database. As results, MT-1 and MT-2 mRNA were found to be expressed in cadmium non-treated control cells and MT 1 mRNA expression was dose-dependent when leydig cells were treated with cadmium chloride. But MT-3 which is known to be brain specific and MT-4 which is another isoform of metallothionein, were not expressed. Other genes induced or depressed in cadmium treated leydig cells were also identified by microarray techniques.

4-Nonylphenol Increased NO Synthesis via a Non-genomic Action in GH3 Cells (뇌하수체 세포인 GH3세포에서 non-genomic action을 통한 Nonylphenol의 nitric oxide 증진효과)

  • Lee Kyung-Jin;Choi Chul-Yung;Sohn Hyun-Jung;Jeong Back-Jin;Moon So-Hee;Lee Hwanghee;Lee Jong-Bin
    • Environmental Analysis Health and Toxicology
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    • v.18 no.4
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    • pp.249-254
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    • 2003
  • 본 연구는 환경호르몬(endocrine disruptors)으로 분류되었으며, 에스트로젠 화합물의 특성을 지닌 4-Nonylphenol (NP)이 설치류 Pituitary 세포 중 성장호르몬을 분비하는 GH3 세포의 Nitric oxide(NO)을 증가시키는 작용기전을 규명코자 수행되었다 먼저 GH3세포에 NP처리 농도에 따른 NO의 생성을 측정한 결과 NP처리농도 의존적으로 증가시켰다. 이러한 NO의 증가가 genomic action인지를 확인하기 위해 GH3세포의 NO를 증가시키는 효소인 neuronal oxide synthase의 단백질량을 측정한 결과 GH3세포에서 NP에 의한 nNOS의 단백질의 변화는 없었다. 에스트로젠 화합물인 NP가 에스트로젠 리셉터 (ER)와의 관계를 조사하기 위해 ER억제제(ICI 168,780)클 처리한 경우 NP에 의해 증가한 NO가 감소하였다. 또한 유전자 전사억제제인 actinomycin D 및 단백질 발현 억제제인 cycloheximide을 처리한 경우는 NP에 의한 NO 증가억제효과가 없었다. 이러한 결과를 종합해 볼 때 GH3 세포에서 NP는 ER을 매개한 non-genomic action에 의해 NO를 증가키는 것으로 사료된다.

Early Life Stage Toxicity of 2,3,7,8,-Tetrachlorodibenzop-Dioxin(TCDD) in Goldfish(Carassius auratus) (금붕어 수정난의 2,3,7,8-TCDD 노출에 따른 다이옥신 관련 유전자의 발현 및 형태학적 변화)

  • Oh, Seung-Min;Ryu, Byung-Taek;Kim, Ha-Ryong;Chung, Kyu-Hyuck
    • Environmental Analysis Health and Toxicology
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    • v.24 no.1
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    • pp.1-8
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    • 2009
  • In this study, we obtained the fertilized eggs from goldfish(Carassius auratus) and observed normal developmental stage(from fertilized eggs to larvae) in non-exposed groups. Goldfish embryos at 3 h postfertilization(hpf) were statically exposed for 1 h to either dimethylsufoxide(DMSO, 0.1%, v/v) or TCDD($0.5{\mu}g/L$). Toxicity and morphological changes were characterized from 3 to 120 h postfertilization(hpf). Egg mortality($0{\sim}48$ hpf) and hatching ratio($72{\sim}83$ hpf) in TCDD-exposed group were significantly different from control groups. However, pericardial edema was first observed at 72 hpf, followed by the onset of yolk sac edema and mortality. In addition, goldfish embryos-larvae exposed to TCDD significantly increased TCDD-related gene such as CYP1A($24{\sim}72$ hpf) and AhR2(72 hpf). This is the first study about in-depth characterization of TCDD-induced developmental toxicity in goldfish(Carassius auratus).

Study on the Moisturizing Effects of Puerariae Radix Ethanol Extract (갈근 에탄올 추출물의 피부 보습 효과에 대한 연구)

  • Hong, Chul-Hee;Lee, Sung-Jin
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.30 no.1
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    • pp.106-117
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    • 2017
  • Objectives : 갈근의 피부 보습 효과에 대해 알아보기 위해 본 연구를 진행하였다. Methods : HaCaT 세포주에 갈근 에탄올 추출물을 처리하였고 Retinoic Acid $1{\mu}M$을 양성 대조군으로 사용하였다. MTT assay, RT-PCR, Hyaluronidase enzyme assay, HA-ELISA kit를 통해 Hyaluronic Acid의 합성량, Hyaluronidase 저해율, 농도별 Hyaluronic Acid 생성량을 측정하였다. 더불어 실제로 피부에 도포 시 보습 능력이 있는지 등에 대하여 확인하였다. Results : 갈근 에탄올 추출물은 뚜렷한 세포독성을 나타내지는 않았고, 모든 농도에서 Hyaluronic Acid 합성과 관련된 hyaluronic acid synthase 2 유전자가 발현되었고, 실제로 Hyaluronic Acid가 생성되는 것을 확인하였다. 임상 효능 평가에서는 유의성 있는 결과를 얻을 수는 없었다. Conclusions : 갈근을 한방 외용제로 사용할 때 유의성 있는 효과를 나타낼 수 있을 것으로 기대할 수 있으며, 실험 결과를 토대로 갈근의 최적 사용 농도를 결정하기 위한 추가적 연구와 복합 처방으로 사용했을 경우에 대한 연구가 추가적으로 진행된다면 한방 외용제로서 잠재적인 가치가 있을 것으로 사료된다.