• Title/Summary/Keyword: genetic toxicity

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The analysis of present condition and the method of medical treatment studies on Scolopendrid Herbal Acupuncture (오공약침(蜈蚣藥鍼)에 대한 연구현황분석(硏究現況分析)과 치료법(治療法)에 관한 연구(硏究))

  • Kim, Sung-Chul
    • Journal of Pharmacopuncture
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    • v.9 no.2
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    • pp.113-127
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    • 2006
  • Objectives : We review a result of studies until the present and suggest the method of medical treatment for the clinical treatment of Scolopendrid Herbalacupuncture. Methods : We analysis the paper of the bibliographic studies, the experiment studies and the clinical studies from 2001 developed Scolopendrid Herbalacupuncture and grope for the course of studies. Results : 1. Scolopendrid Herbalacupuncture is proved the clinical safety by the aninmal and human tests. 2. The pharmacological action of Scolopendra subspinipes mutilans L. Koch is anti-convulsive action, analgesic action, lowering blood pressure, anti-inflammatory action, anti-tumor action and microbe inhibition 3. Scolopendrid Herbalacupuncture has been a fine effect to the entrapment neuropathy and inflammatory. 4. Scolopendrid Herbalacupuncture was thought effective on a acute phase and to the excessive symptoms. The Sub-chronic toxicity experiment observing the response after hypodermic medication over 90 days, The Genetic-mutagenic toxity experiment and the clinical effect studies are necessary.

Toxicogenomic 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;Kim, Ick-Young;Ryu, Jae-Chun
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2003.10b
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    • pp.128-128
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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.(omitted)

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Pharmacogenomics in Relation to Tailor-made Drugs

  • Satoh, Tetsuo
    • Biomolecules & Therapeutics
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    • v.14 no.4
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    • pp.183-188
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    • 2006
  • The field of cytochrome P450 pharmacogenomics has progressed rapidly during the past 25 years. Recently, conjugating enzymes including sulfotransferase, acetyltransferase, glucuronosyltransferase and glutathione transferase have been also extensively studied. All the major human drug-metabolizing P450 enzymes and some conjugating enzymes have been identified and cloned, and the major gene variants that cause inter-individual variability in drug response and are related to adverse drug reactions have been identified. This information now provides the basis for the use of predictive pharmacogenomics to yield drug therapies that are more efficient and safer. Today, we understand which drugs warrant dosing based on pharmacogenomics to improve drug treatment. It is anticipated that genotyping could be used to personalize drug treatment for vast numbers of subjects, decreasing the cost of drug treatment and increasing the efficacy of drugs and health in general. It is assumed that such personalized P450 gene-based treatment which is so-called tailor(order)-made drug therapy would be relevant for 10-20% of all drug therapy in the future.

Development of Tetracycline-regulated Adenovirus Expression Vector System

  • Son, Kyung-Hwa;Lee, Seung-Hoon;Kim, Jong-Sik;Choi, Jung-Joo;Lee, Je-Ho
    • Journal of Genetic Medicine
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    • v.3 no.1
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    • pp.33-37
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    • 1999
  • Recombinant adenovirus vector systems with strong promoters have been used to achieve high level production of recombinant protein. However, this overexpression system cause some problems such as disturbance of cell physiology and increment of cellular toxicity. Here, we showed a tetracycline-regulated adenovirus expression vector system. Our results showed that the expression level of transgene(p-53) was high and easily regulated by tetracycline. In addition, the maximal gene expression level of the tetracycline-controlled gene expression system was higher than that of the wild type CMV promoter system. Therefore, tetracycline-regulated adenoviral vector system could be applicable for regulatory high-level expression of toxic gene. Also, this system will be useful for functional studies and gene therapy.

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Clinical Aspects and Treatments for Pediatric Inflammatory Bowel Diseases

  • Moon, Jin Soo
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.22 no.1
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    • pp.50-56
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    • 2019
  • The incidence of pediatric inflammatory bowel disease (IBD) is increasing worldwide, especially in the developing countries. It differs from adult disease in clinical manifestations, especially with regard to genetic predisposition in monogenic IBD. Pediatric disease also have a tendency to show more aggressive inflammation and greater extent of lesion. Newer drugs such as anti-tumor necrosis factor ${\alpha}$ have been known to make a difference in treating pediatric IBD. Recent studies suggested that the patients with high risk factors might have some benefits from earlier use of biologics. To achieve treatment goals such as relieving symptoms, optimizing growth, and improving quality of life while minimizing drug toxicity, more research is needed to develop tools for risk stratification in the use of biologics for pediatric IBD.

Mitophagy stimulation as a novel strategy for the treatment of mitochondrial diseases

  • Kang-Min Lee;Jeanho Yun
    • Journal of Genetic Medicine
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    • v.19 no.2
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    • pp.49-56
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    • 2022
  • Mitophagy, the selective degradation of damaged or surplus mitochondria using core autophagy machinery, plays an essential role in maintaining cellular mitochondrial function. Impaired mitophagy is closely linked to various human diseases, including neurodegenerative diseases, cardiovascular diseases, cancers and kidney disease. Defective mitophagy induces the accumulation of damaged mitochondria and thereby results in a decline in cellular survival and tissue function. Accordingly, enhancement of mitophagy has been proposed as a novel strategy for the treatment of human diseases closely linked to mitochondrial dysfunction. Recent studies showing that the stimulation of mitophagy has a therapeutic effect on several disease models highlight the possibility of disease treatment using mitophagy. The development of mitophagy inducers with toxicity and the identification of molecular mechanisms will enable the clinical application of mitophagy-based treatments.

Drug Discovery Perspectives of Antisense Oligonucleotides

  • Yeonjoon Kim
    • Biomolecules & Therapeutics
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    • v.31 no.3
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    • pp.241-252
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    • 2023
  • The era of innovative RNA therapies using antisense oligonucleotides (ASOs), siRNAs, and mRNAs is beginning. Since the emergence of the concept of ASOs in 1978, it took more than 20 years before they were developed into drugs for commercial use. Nine ASO drugs have been approved to date. However, they target only rare genetic diseases, and the number of chemistries and mechanisms of action of ASOs are limited. Nevertheless, ASOs are accepted as a powerful modality for next-generation medicines as they can theoretically target all disease-related RNAs, including (undruggable) protein-coding RNAs and non-coding RNAs. In addition, ASOs can not only downregulate but also upregulate gene expression through diverse mechanisms of action. This review summarizes the achievements in medicinal chemistry that enabled the translation of the ASO concept into real drugs, the molecular mechanisms of action of ASOs, the structure-activity relationship of ASO-protein binding, and the pharmacology, pharmacokinetics, and toxicology of ASOs. In addition, it discusses recent advances in medicinal chemistry in improving the therapeutic potential of ASOs by reducing their toxicity and enhancing their cellular uptake.

Cadmium Tolerance in Alfalfa is Related to the Up-regulation of Iron and Sulfur Transporter Genes along with Phytochelatin Accumulation

  • Lee, Ki-Won;Lee, Sang-Hoon;Song, Yowook;Ji, Hee Jung;Choi, Bo Ram;Lim, Eun A;Rahman, Md Atikur
    • Journal of The Korean Society of Grassland and Forage Science
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    • v.40 no.3
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    • pp.190-195
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    • 2020
  • Cadmium (Cd) toxicity is a serious limitation for agricultural production. In this study, we explored tolerance mechanism associated with Cd toxicity tolerance in alfalfa plants. We used three distinct alfalfa cultivars M. sativa cv. Vernal, M. sativa cv. Zhung Mu, and M. sativa cv. Xing Jiang Daye in this study. Cd showed declined chlorophyll score in Xing Jiang Daye compared with Zhung Mu and Vernal. No significant change observed among the cultivars for root and shoot length. Atomic absorption spectroscopy analysis demonstrated a significant accumulation of Cd, Fe, S and PC in distinct alfalfa cultivars. However, Zhung Mu and Xing Jiang Daye declined Cd accumulation in root, where Fe, S and PC incremented only in Zhung Mu. It suggests that excess Cd in Zhung Mu possibly inhibited in root by the increased accumulation of Fe, S and PC. This was further confirmed by the response of Fe (MsIRT1) and S transporters (MsSULTR1;2 and MsSULTR1;3), and MsPCS1 genes associated with Fe, S and PC availability and translocation in roots and shoots. It suggests that specially the transcript signal inducing the responses to adjust Cd especially in Zhung Mu. This finding provides the essential background for further molecular breeding program for forage crops.

Prediction of Non-Genotoxic Carcinogenicity Based on Genetic Profiles of Short Term Exposure Assays

  • Perez, Luis Orlando;Gonzalez-Jose, Rolando;Garcia, Pilar Peral
    • Toxicological Research
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    • v.32 no.4
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    • pp.289-300
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    • 2016
  • Non-genotoxic carcinogens are substances that induce tumorigenesis by non-mutagenic mechanisms and long term rodent bioassays are required to identify them. Recent studies have shown that transcription profiling can be applied to develop early identifiers for long term phenotypes. In this study, we used rat liver expression profiles from the NTP (National Toxicology Program, Research Triangle Park, USA) DrugMatrix Database to construct a gene classifier that can distinguish between non-genotoxic carcinogens and other chemicals. The model was based on short term exposure assays (3 days) and the training was limited to oxidative stressors, peroxisome proliferators and hormone modulators. Validation of the predictor was performed on independent toxicogenomic data (TG-GATEs, Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System, Osaka, Japan). To build our model we performed Random Forests together with a recursive elimination algorithm (VarSelRF). Gene set enrichment analysis was employed for functional interpretation. A total of 770 microarrays comprising 96 different compounds were analyzed and a predictor of 54 genes was built. Prediction accuracy was 0.85 in the training set, 0.87 in the test set and increased with increasing concentration in the validation set: 0.6 at low dose, 0.7 at medium doses and 0.81 at high doses. Pathway analysis revealed gene prominence of cellular respiration, energy production and lipoprotein metabolism. The biggest target of toxicogenomics is accurately predict the toxicity of unknown drugs. In this analysis, we presented a classifier that can predict non-genotoxic carcinogenicity by using short term exposure assays. In this approach, dose level is critical when evaluating chemicals at early time points.

Evaluation of the Genetic Toxicity of Synthetic Chemicals (IV) - Chromosomal Aberration Assay With 11 compounds in Chinese Hamster Lung Cells in vitro -

  • Kim, Kyung-Ran;Kim, Hyun-Joo;Kim, Min-Hee;Youn, Ji-Youn;Kwon, Oh-Seung;Ryu, Jea-Chun
    • Proceedings of the Korea Society of Environmental Toocicology Conference
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    • 1996.12a
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    • pp.63-63
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    • 1996
  • We performed chromosomal aberration assay in Chinese Hamster Lung (CHL) cells in vitro to evaluate theclastogenicity of 11 synthetic chemicals which were listed in Toxicity Evaluation Program of Ministry of Environment of Republic of Korea in 1996. All of the chemicals were carried out MTT assay to determine the 50% cell growth inhibition concentration. All compounds were tested with and without metabolic activation system. Benzoyl chloride revealed positive result at $43\;\mu\textrm{g}/m{\ell}$ in the presence of metabolic activation system, and at 30.8, 61.5 and $123\;\mu\textrm{g}/m{\ell}$ in the absence of metabolic activation system. And p-phenoxy ethanol was observed as positive with the metabolic activation system, but negative without metabolic activation system. Especially 2-propyn-l-ol showed high frequency of pulverization and showed critical difference of cytotoxicity between with and without S9 mixture. Pulverizatiuon is not included in the frequency of structural aberration in our criteria. Dicyclopentadiene, methacrylic acid, aa-dimethylbenzyl hydroperoxide, benzylbutyl phthalate, and p-chlorophenal were revealed negative results.esults.

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