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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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The Korean Society of Toxicology
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Volume 22, Issue 4 - Dec 2006
Volume 22, Issue 3 - Sep 2006
Volume 22, Issue 2 - Jun 2006
Volume 22, Issue 1 - Mar 2006
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Association Study between the Genetic Variants of the Human Atrial Natriuretic Peptide Gene and Essential Hypertension in Korean Population
Bae Joon-Seol ; Kang Byung-Yong ; Lee Kang-Oh ; Lee Seung-Taek ;
Toxicological Research, volume 22, issue 2, 2006, Pages 69~74
Hypertension leads to major health problems in many industrialized countries, and multiple etiologic factors are involved in the pathogenesis of this disorder. The genetic components of the natriuretic peptide system might be involved in the pathogenesis of hypertension. In this regard, the atrial natriuretic peptide (ANP) gene has been proposed as a candidate hypertension gene. Therefore, we investigated the G1837A and C-664G polymorphisms of the ANP gene in 143 Korean normotensives and 118 hypertensives. There were no significant differences in the genotype and allele frequencies between the two groups. Although the frequencies in each of these polymorph isms were not significantly different between normotensives and hypertensives, our results provide additional ethnic information for linkage analysis and associated studies of this disorder with cardiovascular disease.
Assessment of DNA Damage using an Alkaline Single Cell Gel Electrophoresis (SCGE) Comet Assay and Toxic Effects in Chickens by T-2 Toxin Treatment
Hah Dae-Sik ; Heo Jung-Ho ; Lee Kuk-Cheon ; Cho Myung-Heui ; Kim Kuk-Hun ; Kim Chung-Hui ; Lue Jae-Du ; Lee Seung-Hwan ; Kim Gon-Sup ; Kim Eui-Gyung ; Kim Jong-Shu ;
Toxicological Research, volume 22, issue 2, 2006, Pages 75~85
This study was designed to evaluate the possible DNA damaging effects of T-2 toxin using an alkaline single cell gel electrophoresis (SCGE) comet assay and also to investigate toxic effects in chickens. A total of 20 chickens were used in these experiments. Graded concentrations of dietary T-2 toxin (0, 4, 8, and
of diet) were given to groups of 5 broiler chickens. In comet assay, The DNA damage was analysed by the tail extent moment (TEM) and tail length (TL), which were used as markers of DNA strand breaks in SCGE. A significant dose-dependent increase in the extent of DNA migration as well as in the percentage of cells with tails was observed after treatment with T-2 toxin (P<0.05). Treatment with the low T-2 toxin (
of diet) induced a relatively low level of DNA damage in comparison with the high T-2 toxin (
of diet) group. The growth rate was significantly reduced by concentrations of 8, and
of diet (P < 0.05). The feed conversion ratio were significantly affected by any concentrations (P < 0.05). The relative weight of the spleen, and lung was decreased by the growth inhibitory concentrations. The bursa of Fabricius, thymus, and kid- ney were decreased in relative weight by concentrations of
of diet. The relative weight of the liver and heart were unaffected. The hemoglobin (Hb), hematocrit (HCT), and mean corpuscular hemoglobin (MCH) were decreased at concentration of
of diet. As compared with control chickens, there was no marked change in serum components except uric acid in T-2 treated chickens. All lymphoid tissues retained atrophic and lymphoid cell depletion throughout the three weeks trial.
Gene Expression Analysis of Phenylbutazone-induced Liver Damage in Mice
Lee Eun-Ju ; Jeong In-Hye ; Kim Han-Na ; Chung Hee-Kyoung ; Kong Gu ; Kang Kyung-Sun ; Yoon Byung-Il ; Lee Byeong-Hoon ; Lee Mi-Ock ; Kim Ju-Han ; Kim Hyung-Lae ;
Toxicological Research, volume 22, issue 2, 2006, Pages 87~93
The KFDA (Korea Food & Drug Administration) has performed a collaborative toxico-genomics project since 2003. Its aim is to construct a toxicologenomic database of 12 hepatotoxic compounds from mice livers. Phenylbutazone which is non-steroidal anti-inflammatory drug was assigned. It was administered at low (0.0238 mg/kg) and at high (0.238 mg/kg) dose (5 mice per group) orally to the postnatal 6 weeks ICR mice, then the serum and liver were collected at the indicated time (6, 24 and 72 h) after administration. Serum biochemical markers for liver toxicity were measured and histopathologic studies also were carried out. The gene expression profiling was carried out by using Applied Biosystems 1700 Full Genome Expression Mouse. The 2-way ANOVA was used to find genes that reflected phenylbutazone-induced acute toxicity or dose-dependant changes. By self-organization maps (SOM), we identified groups with unique gene expression patterns, some of them are supposed to be related to phenylbutazone induced toxicity, including lipid metabolism abnormality, oxidative stress, cell death and cytoskeleton destruction.
Early Gene Expression in Mouse Spleen Cells after Exposure to Nickel Acetate
Koh Jae-Ki ; Kim Woo-Hyoung ; Lee Chang-Ho ; Nam Hae-Seon ; Kim Sung-Ho ; Woo Kee-Min ; Lee Sang-Han ;
Toxicological Research, volume 22, issue 2, 2006, Pages 95~102
Exposure to soluble nickel compound produces toxic effects on immune system, but the mechanism of action remains to be elucidated. Differential gene expression was studied to understand the potential molecular mechanism responsible for acute toxicity induced by nickel acetate in spleen cells. We exposed mouse spleen cells to nickel acetate with a nontoxic dose (
) and then extracted total RNA at 6 h and 12 h after exposure. The RNA was hybridized onto 10K mouse oligonucleotide microarrays, and data were analyzed using GeneSpring 7.1. Nickel had a modest effects on expression of many genes, in the range of 1.3-3 fold. The expression profile showed time-dependent changes in expression levels of differentially expressed genes, including some important genes related to cell cycle, apoptosis and DNA repair. In hierarchical cluster analysis of duplicate experiments, 111 genes were screened out. Out of these, 44 genes showing time- dependent up-regulation (>1.5 fold) and 38 genes showing down-regulation (>1.5 fold) at all time points were chosen for further analysis. The change in the expression of three genes (GPX1, GADD45B and FAIM) after nickel treatment was validated using RT-PCR. As a rule, a number of genes appear to be coordinately regulated between cell survival and cell death from nickel toxicity. In conclusion, changes in the gene profile in the spleen after nickel treatment are complex and genes with diverse functions are modulated. These findings will be contributed to the understanding of the complicated biological effects of nickel.
Pretreatment of Macrophages with Paclitaxel Inhibits iNOS Expression
Li Mei-Hong ; Kang Jong-Soon ; Kim Hwan-Mook ; Jeon Young-Jin ;
Toxicological Research, volume 22, issue 2, 2006, Pages 103~107
We demonstrate that paclitaxel, an antitumor agent derived from yew tree, inhibits LPS-induced expression of iNOS gene in RAW 264.7 cells. Previously, paclitaxel has been known to induce iNOS gene expression in macrophages. However, in this report we described that the pre-treatment of macrophages with paclitaxel (
) for 8 h inhibited LPS-induced iNOS gene expression. Pretreatment of RAW 264.7 cells with paclitaxel significantly inhibited LPS-stimulated nitric oxide (NO) production. Western immunoblot of iNOS and RT-PCR analysis showed that the decrease of NO was due to the inhibition of iNOS gene expression in RAW 264.7 cells. Immunocytochemical staining of iNOS further confirmed that pretreatment of macrophages with paclitaxel inhibited macrophage activation. Electrophoretic mobility shift assay showed that paclitaxel inhibited
DNA binding. Collectively, these series of experiments indicate that paclitaxel inhibits iNOS gene expression by blocking
Studies for the Guidance of Safety Pharmacology Studies in Compliance with Good Laboratory Practice
Choi Ki-Hwan ; Park Ki-Sook ; Lee Yun-Hee ; Na Hang-Kwang ; Yun Jae-Suk ; Kim Dong-Sup ; Kim Joo-Il ;
Toxicological Research, volume 22, issue 2, 2006, Pages 109~116
Safety pharmacology studies are conducted to investigated the potential undesirable pharmacodynamic effects of a substance on physiological functions in relation to exposure in the therapeutic range and above. In the International Conference on Harmonisation (ICH), the guideline 'S7A: Safety Pharmacology Studies for Human Pharmaceuticals' has been developed and reached Step 5 of the ICH process in 2001. Now the Korea Food and Drug Administration (KFDA) are going to transfer 'The Guideline for General Pharmacology' into 'The Guideline for Safety Pharmacology'. Safety pharmacology studies should be performed in compliance with Good Laboratory Practice (GLP). Thus, the present paper reviews the Japanese GLP guidelines for pharmaceuticals to help the conduct and inspection of safety pharmacology studies in compliance with GLP. We also reviewed the ICH guidelines 'S7B revised : The Nonclinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolongation) by Human Pharmaceuticals' and 'E14 : The Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-antiarrhythmic Drugs' to apply our drug approval systems.
Single Oral Dose Toxicity Study of Water Extracts of Picrorrhiza Rhizoma In ICR Mice
Lee Hyeung-Sik ; Lee Ik-Gu ; Ku Sae-Kwang ;
Toxicological Research, volume 22, issue 2, 2006, Pages 117~126
This study was conducted to obtain the acute information of the oral dose toxicity of lyophilized water extract of Picrorrhiza Rhizoma (PR) - dried underground stem of Picrorrhiza kurroa, having various pharmacological effects, in male and female mice. In order to calculate 50% lethal dose (
), approximate lethal dose and target organs, test article was administered once by oral gavage to male and female ICR mice at 2000, 1000, 500 and 250 mg/kg. The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after dosing with organ weight and histopathology of 12 types of principle organs. As the results, we could not find any mortality, clinical signs, changes in the body weight and gross findings except for hair loss, a significantly (p<0.05) increase of body weight gains in 2000mg/kg of PR extracts-dosing male group and some sporadic gross findings. In addition, no meaningful changes on the organ weight and histopathology of 12 types of principle organs were detected in the present study except for significantly (p<0.05) but dose independent changes on thymus, spleen and popliteal lymph nodes weights, and some sporadic accidental histopathological findings. The results obtained in this study suggest that the PR extract is non-toxic in mice and is therefore likely to be safe for clinical use. The
and approximate lethal dose of PR extracts in both female and male mice were considered as over 2000 mg/kg.
Teratogenicity Evaluation of 2-Bromopropane Using Rat Whole Embryo Culture
Kim Jong-Choon ; Shin Dong-Ho ; Kim Sung-Ho ; Yang Young-Soo ; Oh Ki-Seok ; Jiang Cheng-Zhe ; Chung Moon-Koo ;
Toxicological Research, volume 22, issue 2, 2006, Pages 127~133
Recently, we have reported that the environmental pollutant 2-bromopropane (2-BP) induces a significant embryo-fetal developmental toxicity in rats. However, the cause of developmental toxicity and the relationship between maternal and developmental toxicities could not be elucidated because the developmental toxicity of 2-BP was observed only in the presence of maternal toxicity The in vitro teratogenicity study using whole embryo culture was carried out to understand the teratogenic properties and the possible mechanism of teratogenicity induced by 2-BP in rats. Rat embryos aged 9.5 days were cultured in vitro for 48 hrs at medium concentrations of 0, 1, 3, or 10 mg/ml of 2-BP. Embryos were evaluated for growth, differentiation, and morphological alterations at the end of the culture period. At 10 mg/ml, 2-BP caused a delay in the growth and differentiation of embryos and an increase in the incidence of morphological alterations, including altered yolk sac circulation, abnormal axial rotation, craniofacial hypoplasia, open neuropore, absent optic vesicle and kinked somites. At 3 mg/ml, only a delay in the growth and differentiation of embryos was observed. There were no adverse effects on embryonic growth and development at the concentration of 1 mg/ml. The results showed that the exposure of 2-BP to rat embryos results in a developmental delay and morphological alterations at dose levels of 3 mg/ml culture media or higher and that 2-BP can induce a direct developmental toxicity in rat embryos.
Thirteen-week Repeated-dose Toxicity Studies of STB-HO-BM in Rats
Song Si-Whan ; Jung Winston ; Hong Dong-Ho ;
Toxicological Research, volume 22, issue 2, 2006, Pages 135~144
This study was performed to evaluate repeated-dose toxicities of STB-HO-BM in Sprague-Dawley rats. STB-HO-BM was administered orally to rats at dose levels of 0, 100, 300 and 1,000 mg/kg/day for 13 weeks. In recent study, there were no dose related changes in mortality, clinical signs, body weight changes, food and water consumption, opthalmoscopy, organ weights, urine analysis, hematological findings, and biochemical examination of all animals treated with STB-HO-BM. Gross and histopathological findings revealed no evidence of specific toxicity related to STB-HO-BM. These results suggest that the oral no observed adverse effect level (NOAEL) of STB-HO-BM may be over 1,000 mg/kg in rats.
Genotoxicity Studies of STB-HO-BM, a Germanium Complex
Song Si-Whan ; Jung Winston ; Hong Dong-Ho ;
Toxicological Research, volume 22, issue 2, 2006, Pages 145~151
We have investigated the genotoxicity of STB-HO-BM using in vitro and in vivo system such as Ames reverse mutation test, chromosomal aberration test and micronucleus test. in Ames reverse mutation test, STB-HO-BM treatment at the dose range up to 5,000 ug/plate did not induce mutagenicity in Salmonella typhimurium TA98, TA100, TA102, TA1535, TA 1537 and in Escherichia coli WP2 uvrA with and without metabolic activation. Any significant aberration wasn't observed in chinese hamster lung (CHL) fibroblast cells treated with STB-HO-BM at the concentration of 12.5, 2.5, 5 mg/ml both in the absense and presence of metabolic activation system. In mouse micrnucleus test, no significant increase in the occurrence of micronucleated polychromatic erythrocytes was observed in ICR male mice orally administered with STB-HO-BM at the doses of 0.5, 1.0, 2.0 g/kg. These results indicate that STB-HO-BM has no mutagenic potential under the condition in this study.
Single Dose Toxicity Studies of STB-HO-BM in Rats and Dogs
Song Si-Whan ; Jung Winston ; Hong Dong-Ho ;
Toxicological Research, volume 22, issue 2, 2006, Pages 153~156
The acute toxicity of STB-HO-BM was evaluated in Sprague Dawley (SS) rats and beagle dogs. STB-HO-BM was administered orally to rats at dose levels of 0 and 2,000mg/kg/day and to dogs at dose levels of 0, 500, 1,000 and 2,000 mg/kg/day. In these experiments, there were no death and clinical changes which were related to STB-HO-BM administration. In addition, there were no significant changes between control and treated groups in body weights and autopsy findings. In conclusion, the administration of STB-HO-BM 2,000 mg/kg in SD rats and up to 2,000mg/kg in beagle dogs was proved to be safe, and it is thought that STB-HO-BM may not show any toxicity in its clinical use.