• Title/Summary/Keyword: BIOLOGICAL TOXICITY

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DNA Microarrays Analysis of Gene Expression Profiles in Diabetes-related genes using Immunosuppressant (면역억제제에 의한 당뇨 관련 유전자의 DNA microarray 분석)

  • Kim, Kyoung-Shin;Kim, Byoung-Soo
    • Journal of Haehwa Medicine
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    • v.21 no.1
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    • pp.11-21
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    • 2012
  • New onset diabetes is a major complication after kidney transplantation. However, the natural course of posttransplantation diabetes mellitus (PTDM) remains unclear. The aim of this study was to demonstrate the detailed natural courses of PTDM according to the onset and persistency of hyperglycemia, and to investigate risk factors for development of different courses of PTDM in renal allograft recipients. The purpose of this study is to develop novel immune suppressants for PTDM using of action mechanism of them. The use of immunosuppressive drugs in transplanted patients is associated with the development of diabetes, possibly due to ${\beta}$-cell toxicity. To better understand the mechanisms leading to post-transplant diabetes, we investigated the actions of prolonged exposure of ${\beta}$-cells to therapeutical levels of tacrolimus (FK506) or cyclosporin A(CsA). The immunosuppressive drug cyclosporine(CsA) is a potent agent widely used after organ transplantations and various autoimmune disorders. After using CsA, some patients suffer severe complications including renal and vascular toxicity. The renal or vascular toxicity is influenced by the degree of the endothelial damage. FK506(tacrolimus) is a widely used immunosuppressive agent in the treatment of various medical conditions, including autoimmune disease, bone marrow and organ transplantations. We found some interesting clusters and confirmed the feasibility of cDNA microarray in the study of Immunosuppressant. In this study, we investigated gene expression patterns induced by Immunosuppressant in RIN-m5F of rat insulinoma cell line. Gene expressions evaluated using cDNA microarry in two clusters were increased or decreased. this study provides comprehensive comparison of the patterns of gene expression changes induced by CsA and FK506 in ${\beta}$-cells. This study could establish that the mode of action mechanism by which currently used insulin inhibitors inducing PTDM could be elucidated at least in part, which raises the possibility that novel immune suppressive PTDM can be developed. The molecular biological study on PTDM will also contribute the progress in diabetes research field as well as in that of PTDM.

Alleviating Effects of Vitamin C on the GRamoxone Toxicity in Rat Liver (흰쥐 간조직에 미치는 제초제 Gramoxone 독성에 대한 비타민 C의 완화 효과)

  • Un-Bock Jo;Sung-Ro Kim
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.23 no.3
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    • pp.380-386
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    • 1994
  • The behavior of glycogen and histological changes of hepatic tissues in the liver of rats, aged 6 to 7 weeks, fed 18% casein diet under control, gramoxone and gramoxone + vitamin C(Vt. C) diets has been investigated in a comined histropathological and histochemical studies. Cloudy swelling and fat changes of hepatic cells were observed in the gramoxone group with the duration of feeding time. Fat changes of hepatic cells were observed more obviously than cloudy welling, especially in the hepatic cells of periportal area. The number of Kupffer's cells increased signifciantly in the gramoxone group fed for 4weeks. The cloudy swelling and fat changes decreased obviously in the gramxone + Vt. C group. Glycogen content of heaptic cells tended to increase slightly in the gramoxone group as compared with the control group . moreover, glycogen depositons were higher in the hepatic cells where fat changes were obvious. It seems to be that Vt.C alleviating effects on the gramoxone toxicity in the patterns of glycogen distribution and histological structure of heaptic tissues.

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A New Methodology of Measuring Water Toxicity using Sulfur Oxidizing Bacteria (황산화미생물을 이용한 새로운 수(水)중 생태독성탐지 방법)

  • Oh, Sang-Eun
    • Journal of Korean Society of Environmental Engineers
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    • v.32 no.6
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    • pp.555-562
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    • 2010
  • For the rapid and reliable detection of toxic compounds in water, a novel toxicity detection methodology based on sulfur-oxidizing bacteria (SOB) has been developed. The methodology exploits the ability of SOB to oxidize elemental sulfur to sulfuric acid in the presence of oxygen. The reaction results in an increase in electrical conductivity (EC) and a decrease in pH. Using a synthetic stream water (EC=0.12 mS/cm and pH=7.2), the baseline steady-state EC and pH values were 0.5~1.2 mS/cm and ~2.5 over 7 days of testing at HRT 30 minutes. When nitrite compounds were added to the system, the effluent EC decreased and the pH increased due to the inhibition of the SOB. Optimum HRT was 30 min and this HRT could be decresed by using smaller sulfur particles.

Studies on the Structure and Biological Activity of Microcystins Produced from Korean Cyanobacteria, Microcystis Species (한국산 남조류 Microcystis로부터 생산된 microcystin 구조와 생물활성에 관한 연구)

  • Choi, Byoung Wook;Noh, Young Ho;Lee, Jong-Soo
    • Applied Chemistry for Engineering
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    • v.8 no.4
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    • pp.610-616
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    • 1997
  • Hepatotoxic cyanobacteria, Microcystis species, were collected from the Nakdong River and we could isolate hepatotoxins, microcystin-LR and microcystin-RR, which are also strong inhibitors of protein phosphatase 1 and 2A. From the microcystins, several microcystin derivatives were synthesized and tested on the mouse toxicity in order to establish the structure-activity relationship. Esterification od carboxyl groups of Glu and MeAsp residue produced nontoxic compounds. However, when we reduced the Mdha residue with sodium borohydride into Ala residue, toxicity was still maintained. Also, the change of guanidyl moiety of Arg residue in microcystin-LR into dimethylpyrimidyl moiety did not change the toxicity of microcystins as well. Thus the carboxyl groups seem to play important roles in binding with protein phosphatase 1 and 2A, whereas Mdha residue and the guanidyl moiety of Arg residue do not.

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Toxicogenomics Study on TK6 Human Lymphoblast Cells Treated with Mitomycin C

  • Kim, Joo-Hwan;Koo, Ye-Mo;Lee, Woo-Sun;Suh, Soo-Kyung;Kang, Jin-Seok;Han, Eui-Sik;Kim, Seung-Hee;Park, Sue-N.
    • Molecular & Cellular Toxicology
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    • v.3 no.3
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    • pp.165-171
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    • 2007
  • Mitomycin C (MMC), an antitumor antibiotic isolated from Streptomyces caespitosus, is used in chemotherapy of gastric, bladder and colorectal cancer. MMC is activated in vivo to alkylate and crosslink DNA, via G-G interstrand bonds, thereby inhibiting DNA synthesis and transcription. This study investigates gene expression changes in response to MMC treatment in order to elucidate the mechanisms of MMC-induced toxicity. MMC was admistered with single dose (0.32 and 1.6 ${\mu}M$) to TK6 cells. Applied Biosystem's DNA chips were used for identifying the gene expression profile by MMC-induced toxicity. We identified up- or down-regulated 90 genes including cyclin M2, cyclin-dependent kinase inhibitor 1A (p21, cip1), programmed cell death 1, tumor necrosis factor (ligand) superfamily, member 9, et al. The regulated genes by MMC associated with the biological pathways apoptosis signaling pathway. Further characterization of these candidate markers related to the toxicity will be useful to understand the detailed mechanism of action of MMC.

Biodegradation of Potential Diesel-Oxygenate Additive Including DBM(DiButyl Maleate) (DBM(DiButyl Maleate)을 포함한 잠재적 디젤첨가제 생분해특성)

  • Chang, Soonwoong
    • Journal of the Korean GEO-environmental Society
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    • v.11 no.8
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    • pp.65-71
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    • 2010
  • In this study, we have evaluated biodegradability of diesel-oxygenates including DBM and gasoline-oxygenates having similar physio-chemical properties using indigenous aerobic microorganisms from a diesel-contaminated soil. Toluene and Ethanol have shown higher biological activity and the first-order degradation rate constants ranged around $0.11{\sim}0.3day^{-1}$. However, MTBE, gasoline-oxygenate has shown as a limited substrate. Moreover, As increased initial concentrations of DBM and TGME, degradation rates of those were decreased relatively. As a strategy to evaluate biodegradability of DBM and TGME, reduction of diesel-oxygenates, $CO_2$ production and toxicity by algae were monitored. This results indicated possible mineralization of diesel-oxygenates, But we could predict that residual byproduct produced even though complete consumption of diesel-oxygenates were observed if algal toxicity variation considered. In conclusion, it is the first report that diesel-oxygenates including DBM could be biodegraded effectively by indigenous soil microorganisms and this result increased the possibility of bioremediation technology to apply into oil-contaminated sites.

Gene Expression Analysis for Statin-induced Cytotoxicity from Rat Primary Hepatocytes

  • Ko, Moon-Jeong;Ahn, Joon-Ik;Shin, Hee-Jung;Kim, Hye-Soo;Chung, Hye-Joo;Jeong, Ho-Sang
    • Genomics & Informatics
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    • v.8 no.1
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    • pp.41-49
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    • 2010
  • Statins are competitive inhibitors of hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase and used most frequently to reduce plasma cholesterol levels and to decrease cardiovascular events. However, statins also have been reported to have undesirable side effects such as myotoxicity and hepatotoxicity associated with their intrinsic efficacy mechanisms. Clinical studies recurrently reported that statin therapy elevated the level of liver enzymes such as ALT and AST in patients suggesting possible liver toxicity due to statins. This observation has been drawn great attention since statins are the most prescribed drugs and statin-therapy was extended to a larger number of high-risk patients. Here we employed rat primary hepatocytes and microarray technique to understand underlying mechanism responsible for statin-induced liver toxicity on cell level. We isolated genes whose expressions were commonly modulated by statin treatments and examined their biological functions. It is of interest that those genes have function related to response to stress in particular immunity and defense in cells. Our study provided the basic information on cellular mechanism of statin-induced cytotoxicity and may serve for finding indicator genes of statin -induced toxicity in rat primary hepatocytes.

A Study for Bioassay on the HBr Combustion Toxity (생물학적 분석을 통한 HBr의 연소 독성에 관한 연구)

  • Cho, Nam-Wook;Shin, Hyun-Joon;Lee, In-Ku;Oh, Eun-Ha
    • Journal of the Korean Applied Science and Technology
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    • v.29 no.4
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    • pp.545-551
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    • 2012
  • Due to the use of polymeric materials in construction materials, the fire combustion gases that occur in the fire are various. The one of combustion gases, HBr is measured to evaluate the toxicity of the combustion gases in the FTP Code Part 2, Standard NES 713 and Standard BS 6853. According to the MSDS, Inhalation of HBr gas especially cause burn, respiratory dysfunction, headache, etc. The people who are exposed to 50ppm of HBr gas, very irritant gas may also frequently result in both immediate death and post-exposure deaths due to pulmonary complications. In this paper, we conduct a research on the combustion toxicity of HBr gas hazardous test which is motility measurement of the mice exposed to the HBr standard gas comparing the biological analysis result.

Review of Nanoparticles in Drinking Water: Risk Assessment and Treatment (나노입자의 현황조사 및 처리방안 마련을 위한 문헌연구)

  • Kim, Seung-Hyun;Hong, Seung-kwan;Yoon, Je-Yong;Kim, Doo-Il;Lee, Sang-Ho;Kweon, Ji-Hyang;Kim, Hyung-Soo;ko, Seok-Dock;Kuk, Ji-Hoon
    • Journal of Korean Society of Water and Wastewater
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    • v.25 no.2
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    • pp.201-212
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    • 2011
  • Nanotechnology is the applied science which develops new materials and systems sized within 1 to 100 nanometer, and improves their physical, chemical, and biological characteristics by manipulating on an atomic and molecular scale. This nanotechnology has been applied to wide spectrum of industries resulting in production of various nanoparticles. It is expected that more nanoparticles will be generated and enter to natural water bodies, imposing great threat to potable water resources. However their toxicity and treatment options have not been throughly investigated, despite the significant growth of nanotechnology-based industries. The objective of this study is to provide fundamental information for the management of nanoparticles in water supply systems through extensive literature survey. More specifically, two types of nanoparticles are selected to be a potential problem for drinking water treatment. They are carbon nanoparticles such as carbon nanotube and fullerene, and metal nanoparticles including silver, gold, silica and titanium oxide. In this study, basic characteristics and toxicity of these nanoparticles were first investigated systematically. Their monitoring techniques and treatment efficiencies in conventional water treatment plants were also studied to examine our capability to mitigate the risk associated with nanoparticles. This study suggests that the technologies monitoring nanopartilces need to be greatly improved in water supply systems, and more advanced water treatment processes should be adopted for better control of these nanoparticles.

Influence of Heavy Metals, Ammonia, and Organotin Compounds on the Survival of Arkshell Clams, Scapharca broughtonii (중금속, 암모니아, 유기주석화합물이 피조개 (Scapharca broughtonii) 의 생존에 미치는 영향)

  • Kim, Chan-Kook;Kim, Dong-Hoon;Lee, Jung-Suk;Lee, Kyu-Tae
    • The Korean Journal of Malacology
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    • v.20 no.1
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    • pp.93-105
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    • 2004
  • Arkshell clams, Scapharca broughtonii, are economically important edible bivalves and widely cultivated in the Southern coast of Korea. Recently, the production of S. broughtonii has been dramatically decreased and various reasons including chemical pollution were suspected to be related to the production declines. However, it remains unknown whether the chemical pollution levels of the surrounding environments were high enough for the biological and ecological disturbance for the population of S. broughtonii, because no systematic toxicological study using S. broughtonii has been conducted previously. In the present study, we exposed arkshell clams, S. broughtonii to various waterborne pollutants including heavy metals (Cd, Cu and Hg), ammonia and organotins (tributyltin and triphenyltin) to determine the effect concentrations of these pollutants for the survival of S. broughtonii for 20 days. The median lethal concentrations ($LC_50$) of S. broughtonii were 2.1 mg/l for Cd, 0.065 mg/l for Cu, 0.40 mg/l for Hg, 79.4 mg/l for total ammonia (1.9 mg/l for unionized ammonia), 0.5 ${\mu}$g/l for TBT, and 14${\mu}$g/l for TPhT. Lethal toxicity of the most pollutants increased with both exposure duration and concentration. The toxicity of TBT was greatest for S. broughtonii, followed by TPhT > Cu > Hg > Cd > ammonia. The sensitivities of S. broughtonii to heavy metals and TBT were comparable to those of other aquatic organisms, but they were relatively tolerable to ammonia. The environmental concentrations of the tested pollutants were compared with the effect concentrations of those for the survival of S. broughtonii to assess the potential risks of the pollutants in the field conditions.

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