• 제목/요약/키워드: genetic toxicology

검색결과 252건 처리시간 0.024초

Secondary Fish-Odor Syndrome Can be Acquired by Nitric Oxide-mediated Impairment of Flavin-containing Monooxygenase in Hepatitis B Virus-Infected Patients

  • Yi, Hyeon-Gyu;Lee, Jung-Nam;Ryu, Seung-Duk;Kang, Ju-Hee;Cha, Young-Nam;Park, Chang-Shin
    • The Korean Journal of Physiology and Pharmacology
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    • 제8권4호
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    • pp.213-218
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    • 2004
  • Primary fish-odor syndrome (FOS) is a genetic disorder caused by defective flavin-containing mono-oxygenase 3 gene (FMO3) with deficient N-oxidation of trimethylamine (TMA), causing trimethylaminuria (TMAU). By contrast, secondary FOS can be acquired by decreased FMO activities in patients with chronic liver diseases, but the underlying mechanisms are unknown. In the present study, we examined plasma NOx concentrations and viral DNA contents as well as in vivo FMO activities and their correlations in chronic viral hepatitis (CVH) patients. Plasma concentration of NOx was significantly increased by 2.1 fold $(56.2{\pm}26.5\;vs.\;26.6{\pm}5.4\;{\mu}M,\;p<0.01)$, and it was positively correlated with plasma hepatitis B virus (HBV) DNA contents $(r^2=0.2838,\;p=0.0107)$. Furthermore, the elevated plasma NOx values were inversely and significantly correlated with in vivo FMO activities detected by ranitidine-challenged test $(8.3%\;vs.\;20.0%,\;r^2=0.2109,\;p=\0.0315)$. TMA N-oxidation activities determined in CVH patients without challenge test were also significantly low (73.6% vs. 95.7%, p< 0.05). In conclusion, these results suggested that secondary FOS could be acquired by the endogenously elevated NO in patients with CVH.

Altered Gene Profiles using KISTCHIP-400 in MCF-7 cells after Exposure to Di(2-ethylhexyl) Phthalate (DEHP) and Dibutyl Phthalate (DBP)

  • Yun, Hye-Jung;Kim, Youn-Jung;Kim, Eun-Young;Ryu, Jae-Chun
    • 한국환경독성학회:학술대회논문집
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    • 한국환경독성학회 2003년도 추계국제학술대회
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    • pp.174-174
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    • 2003
  • There are many synthetic chemicals, such as di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP), used in chemical reaction processes in industry. The establishment of toxicity and detection of synthetic chemicals that may pose a genetic hazard in our enviornment is subjects of great concern at present DEHP, a ubiquitous phthalate plasticizer, induces a wide range of developmental and reproductive toxicities in mammals. DEHP belongs to the large diverse class of peroxisome proliferator compounds, which include herbicides, hypolipidemic drugs. DBP is a plasticizer used to products containing nitrocellulose, polyvinyl acetate, and polyvinyl chloride such as food wraps and blood bags. DBP is also used in cosmetics as a solvent and fixative for perfumes, a suspension agent for solids, an antifoamer, a skin emollient, and hair spray The present study was performed to examine patterns of gene expression in MCF-7 cells following DEHP and DBP exposure. Changes in gene expression were determined by microarray analysis using KISTCHIP-400 including 401 endocrine related genes based on public database and research papers. Of the genes analysis, we determined that genes detected by array showed a 2-fold or greater change in their expression level(increase or decrease). The results of this study demonstrate that a number of genes were differentially expressed in MCF-7 cells but these changes were not significant. Therefore, we keep going this study using microarray analysis and future studies will examine changes of gene expression on time-course and does treatment in variable cell lines.

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TERT rs2736098 Polymorphism and Cancer Risk: Results of a Meta-analysis

  • Qi, Hao-Yu;Zou, Peng;Zhao, Lin;Zhu, Jue;Gu, Ai-Hua
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권7호
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    • pp.3483-3488
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    • 2012
  • Objective: Several studies have demonstrated associations between the TERT rs2736098 single nucleotide polymorphisms (SNPs) and susceptibility to cancer development. However, there are conflicting results. A systematic meta-analysis was therefore performed to establish the cancer risk associated with the polymorphism. Methods: In this meta-analysis, a total of 6 case-control studies, including 5,567 cases and 6,191 controls, were included. Crude odds ratios with 95% confidence intervals were used to assess the strength of associations in several genetic models. Results: Our results showed no association reaching the level of statistical significance for overall risk. Interestingly, in the stratified analyses (subdivided by ethnicity), significantly increased risks were found in the Asian subgroup which indicates the TERT rs2736098 polymorphism may have controversial involvement in cancer susceptibility. Conclusions: Overall, this meta-analysis indicates that the TERT rs2736098 polymorphism may have little involvement in cancer susceptibility.

A Single Nucleotide Polymorphism in Transforming Growth Factor-$\beta$ type II Receptor of the Rat

  • Ryu, Doug-Young
    • Toxicological Research
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    • 제16권1호
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    • pp.59-61
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    • 2000
  • A single nucleotide polymorphism in the transforming growth factor-$\beta$ type II receptor (TGE$\beta$RII) gene of the rat was studied. TGF$\beta$RII is a tumor suppressor that is frequently inactivated by mutation in human colon cancers. A novel nucleotide polymorphism of G to A(or A to G), which causes a silent mutation at codon 129, was found in G:C rich sequence in the TGF$\beta$RII gene of Sprague-Dawley rats. The results suggest that genetic polymorphism occures without a strain of the laboratory animal.

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Quantitative Structure-Activity Relationships for Radical Scavenging Activities of Flavonoid Compounds by GA-MLR Technique

  • Om, Ae-Son;Ryu, Jae-Chun;Kim, Jae-Hyoun
    • Molecular & Cellular Toxicology
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    • 제4권2호
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    • pp.170-176
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    • 2008
  • The quantitative structure-activity relationship (QSAR) of a set of 35 flavonoid compounds presenting antioxidant activity was established by means of Genetic Algorithm-Multiple Linear Regression (GA-MLR) technique. Four-parametric models for two sets of data, the 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging activity $(R^2=0.788,\;Q^2_{cv}=0.699\;and\;Q^2_{ext}=0.577)$ and scavenging activity of reactive oxgen species (ROS) induced by $H_2O_2 (R^=0.829,\;Q^2_{cv}=0.754\;and\;Q^2_{ext}=0.573)$ were obtained with low external predictive ability on a mass basis, respectively. Each model gave some different mechanistic aspects of the flavonoid compounds tested in terms of the radical scavenging activity. Topological charge, H-bonding complex and deprotonation processes were likely to be involved in the radical scavenging activity.

TPA-and $H_2O_2$- induced Apoptosis by Epigenetic Mechanism and Preventive Effect of L-Carnosine on TPA- and $H_2O_2$- induced Apoptosis of v-myc Transformed Rat Liver Epithelial Cells

  • Kang, Kyung-Sun;Yun, Jun-Won;Cho, Sung-Dae;Lee, Yong-Soon
    • 한국독성학회:학술대회논문집
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    • 한국독성학회 2001년도 International Symposium on Signal transduction in Toxicology
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    • pp.22-40
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    • 2001
  • Apoptosis is characterized by DNA fragmentation, chromatin condensation and plasma membrane blebbing. These apoptotic processes have been mainly associated with genetic mechanisms. Recently, these processes have been also associated with mitochondrial events that include the release of cytochrome c and Diablo/SMAC by modulation of mitochondrial membrane permeability.(omitted)

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POLYMORPHISM OF GSTM1, GSTT1, GSTP1, NATII AND CYP1A1 AND THE SUSCEPTIBILITY TO ASTHMA

  • Ahn, Tai-Hui;Kim, Su-Young;Kim, Tai-Yun;Paek, Do-Myung;Chung, Hai-Won
    • 한국독성학회:학술대회논문집
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    • 한국독성학회 2001년도 International Symposium on Signal transduction in Toxicology
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    • pp.112-112
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    • 2001
  • The genetic polymorphism of GSTM1, GSTT1, GSTP1, NATII and CYP1A1 genes among 33 asthma patients and 66 controls were investigated to find the association between the polymorphism and the risk of asthma. The frequency of the GSTT1 null genotype was slightly higher in asthma patients than that in the control, but this difference was not significant.(omitted)

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THE MICROSOMAL EPOXIDE HYDROLASE(MEPHXS) POLYMORPHISMS AND THE ASSOCIATION OF MICRONUCLEI(MN) IN THE BENZENE-EXPOSED WORKERS

  • Kim, Tae-Yon;Kwon, Seul-A;Kim, Jin-Sik;Kim, Su-Young;Lee, Young-Jun;Chung, Eun-Jung;Paek, Do-Myung;Park, Jung-Keun;Chung, Hai-Won
    • 한국독성학회:학술대회논문집
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    • 한국독성학회 2002년도 Current Trends in Toxicological Sciences
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    • pp.134-134
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    • 2002
  • In order to investigate whether genetic polymorphisms in the mEH exon3 (Tyr139His), exon4 (His113Arg) interact with the formation of MN in benzene exposed workers, the PCR-RFLP based genotyping of 76 exposed and 115 controls were performed and cytokinesis-block micronucleus (CBMN) analysis of 56 exposed and 53 controls was employed.(omitted)

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합성화학물질들의 유전독성평가(Ⅸ) -합성 제초제 Pretilachlor - (Evaluation of the Genetic Toxicity of Synthetic Chemicals (Ⅸ) a Synthetic Selective Herbicide, Pretilachlor-)

  • 류재천;김연정
    • Environmental Analysis Health and Toxicology
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    • 제19권1호
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    • pp.93-100
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    • 2004
  • Pretilachlor [2-chloro-N -(2, 6-diethylphenyl)-N-(2-propoxyethyl) acetamide, $C_{17}$H$_{26}$ClNo$_2$, M.W.=311.9, CAS No.51218-49-6]는 제초제의 일종으로 본 연구에서는 박테리아 복귀 돌연변이 시험과 포유동물 세포를 이용한 염색체 이상 시험 및 마우스를 이용한 in vivo소핵 시험을 수행하여 pretilachlor의 유전독성을 평가하였다. 박테리아 복귀 돌연변이 시험에서 pretilachlor는 Salmonella typhimurium TA98, TA 100, TA1535, TA1537 균주의 대사 활성계 존재 및 부재시 313-5,000$\mu\textrm{g}$/plate의 범위에서 농도 의존적인 돌연변이 율의 증가를 관찰할 수 없었다. 또한 포유동물 세포인 Chinese hamster lung (CHL) fibroblast를 이용한 염색체 이상 시험에서 pretilachlor는 대사 활성계 존재 및 부재시 1.56-6.24$\mu\textrm{g}$/mL의 농도에서 clastogenicity를 보이지 않았고, 137.5-550.1 mg/kg의 pretilachlor를 복강 주사한 마우스의 골수세포를 이용한 in vivo소핵 시험의 결과에서도 통계적으로 유의한 소핵 유발능을 관찰할 수 없었다었다

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

  • 류재천;김연정
    • Environmental Analysis Health and Toxicology
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    • 제19권3호
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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.