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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Journal DOI :
The Korean Society of Toxicology
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Volume & Issues
Volume 21, Issue 4 - Dec 2005
Volume 21, Issue 3 - Sep 2005
Volume 21, Issue 2 - Jun 2005
Volume 21, Issue 1 - Mar 2005
Selecting the target year
The Recommended Approaches and Recent Trends in Reproductive and Developmental Toxicology
Kwack, Seung-Jun ; Cho, Dae-Hyun ;
Toxicological Research, volume 21, issue 4, 2005, Pages 271~278
Reproductive and developmental toxicology is concerned with various physical or chemical agents interfering with fertility in both gender or normal growth of offsprings. Reproductive and developmental toxicology is rather a complex science, with many fields, i.e., various endpoints are involved and many different mechanisms of action. For that reason, diverse aspects must be considered when attempting to assess possible adverse health effects in the area of reproductive and developmental toxicology. The thalidomide tragedy made it clear to regulatory authorities around the world that systematic, comprehensive evaluation of the reproductive cycle was needed to adequately evaluate the potential of medicinal drugs to impair the process of reproduction or the development of embryos, fetuses, and children. International Conference on Harmonization of Technical Requirements for the Registration of Pharmaceuticals for Human Use (ICH) and U.S. Food and Drug Administration (FDA) developed a guideline to assess the reproductive and developmental toxicity. Also these guidelines have since been applied to the detection and regulation of environmental toxicants, food additives, and so on. Although it was hoped that testing procedures of guideline would be updated constantly to reflect the current state of the science in reproductive and developmental toxicology, it was not until this decade that regulatory guidelines and testing methods have been altered in a significant way. In this paper, we would like to present the recommended approaches and recent trends for improvement of testing guidelines or experimental methods in reproductive and developmental toxicology.
Protective Activity Against Oxidative Stress of Plants Indigenous to Korea
Jung Myung Sun ; Kang Kyoung Ah ; Zhang Rui ; Chae Sungwook ; Yoo Byoung-Sam ; Yang Young Taek ; Lee Nam Ho ; Park Jae Woo ; Hyun Jin Won ;
Toxicological Research, volume 21, issue 4, 2005, Pages 279~284
We have screened the cytoprotective effect against
radiation induced oxidative stress from 32 Korean plants. Betula ermani var.saitoana (caulis, leaves), Rosa wichuraiana (caulis), Sorbus commixta (caulis), Weigela florida (leaves), Cirsium rhinoceros (whole plant), and Viburnum erosum (caulis) were found to scavenge 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical and intracellular reactive oxygen species (ROS). As a result, extracts of six plants reduced cell death of Chinese hamster lung fibroblast (V79-4) cells induced by
treatment. In addition, these extracts protected cell death of V79-4 cells damaged by
radiation. In addition, these extracts scavenged ROS generated by radiation. Taken together, the results suggest that Betula ermani var. saitoana, Rosa wichuraiana, Sorbus commixta, Weigela florida, Cirsium rhinoceros, and Vibumum erosum protect V79-4 cells against oxidative damage by radiation through scavenging ROS.
Inhibition of p65 Nuclear Translocation by Radicicol, Heat Shock Protein Inhibitor
Kim, Sang-Gyu ; Jeon, Young-Jin ; Lee, Seog-Ki ;
Toxicological Research, volume 21, issue 4, 2005, Pages 285~290
We demonstrate that radicicol, a macrocyclic antifungal antibiotic originally isolated from Monosporium bonorden, inhibits LPS-induced expression of iNOS gene in RAW 264.7 cells. Treatment of peritoneal macrophages and RAW 264.7 cells with radicicol inhibited LPS-stimulated nitric oxide production in a dose-related manner. Immunohistochemical staining of iNOS and RTPCR analysis showed that the decrease of NO was due to the inhibition of iNOS gene expression in RAW 264.7 cells. Immunostaining of p65, EMSA, and reporter gene assay showed that radicicol inhibited
nuclear translocation. DNA binding, and transcriptional activation, respectively. Collectively, these series of experiments indicate that radicicol inhibits iNOS gene expression by blocking
nuclear translocation. Due to the critical role that NO release plays in mediating inflammatory responses, the inhibitory effects of radicicol on iNOS suggest that radicicol may represent a useful anti-inflammatory agent.
Silica Induced Phospholipase D (PLD) Activation in Rat2 Fibroblasts
Ahn Eun-Kyung ; Lim Oh-Kyung ; Nam Hae-Yun ; Kim Hyung Jung ; Chung Namhyun ; Bae Gwi-Nam ; Lim Young ;
Toxicological Research, volume 21, issue 4, 2005, Pages 291~295
To define the effect of silica on the stimulator of signaling pathway, we studied the phospholipase D (PLD) activity in the Rat2 fibroblasts. Silica stimulated the accumulation of labeled
in a time- and concentration-dependent manner. This Silicainduced PLD activity was partially attenuated by the pretreatment with U73122 (phospholipase C inhibitor), genistein (protein tyrosine kinase inhibitor), PD 98056 (MEK inhibitor) and mepacrine (phospholipase
inhibitor). But, sphingosine (protein kinase C inhibitor) and DPI (NADPH reductase inhibitor) had not effect the PLD activity. Silica also increased the PLD activity about four fold, which imply that the PLD activity is more influenced by the mobilization of PLD than other signaling mediators. The PLD activity also partially inhibited calcium chelator EGTA or/and BAPTA/AM compared to silica. Finally, we concluded that a silica-stimulated phospholipase D activity is present in the Rat2 fibroblasts and is modulated by combination of various signaling mediators.
Risk Assessment of Human Exposure to Methidathion during Harvest of Cucumber in Green House
Byoun Ji-Youn ; Choi Hoon ; Moon Joon-Kwan ; Park Hee-Won ; Liu Kwang-Hyeon ; Ihm Yang-Bin ; Park Byeoung-Soo ; Kim Jeong-Han ;
Toxicological Research, volume 21, issue 4, 2005, Pages 297~301
Farmers are generally expressed to pesticides through mixing loding, application activity and harvesting of crop after application of pesticides. The present work investigated the exposure and risk of furathiocarb to workers when harvesting of cucumber was carried out in green house after application of furathiocarb EC. Glove was used for the hand exposure assessment, socks for foot and dermal patches for the other parts of body. Personal air monitor equipped with a XAD-2 resin was used for the respiratory exposure assessment. During the harvest of cucumber in green house, the initial rate of potential dermal exposure (Day 1) for methidathion was 1.3 mg/hr. The major exposure parts were hand
during 3 days' harvest. No exposure was detected from the respiratory monitoring. For risk assessment, the potential dermal exposure (PDE), the absorbable quantity of exposure (AQE) and the margin of safety (MOS) and margin of exposure (MOE) were calculated. In risk assessment of harvester exposure for 7days, all MOS was > 1 and MOE was > 100 indicating that possibility of risk was little.
Cytotoxicity of Copper Nanoparticles in Cultured Human Bronchial Epithelial Cells (BEAS-2B)
Park Eun-Jung ; Park Kwangsik ;
Toxicological Research, volume 21, issue 4, 2005, Pages 303~307
Nanomaterials, which ranges in size from 1 to 100 nm, have been used to create uqnique devices at the nanoscale level possessing novel physical and chemical functional properties. However, the toxicities of nanomaterials have not been fully tested and the risk of nanomaterials is emerging issues in these days. In this study, the cytotoxicity of copper nanoparticles was tested in cultured human bronchial epithelial cells. As a results, copper nanoparticles showed cytotoxicity similar with cupric ion and the apoptotic mechanisms of DNA fragmentation and caspase-3 activation were involved. Induction of heme oxygenase-1 and thioredoxin reductase by copper nanoparticles indicated that cytotoxicity of copper nanoparticles is likely to be mediated through oxidative stress.
Effect of Flavonoid Fractions Extracted from Rhus verniciflua STOKES on the Reproductive Parameters in SD Male Rats
Na Chun-Soo ; Choi Bum-Rak ; Choo Dong-Wan ; Choi Won-Il ; Kim Jin-Bum ; Kim Hyun-Chung ; Park Young In ; Dong Mi-Sook ;
Toxicological Research, volume 21, issue 4, 2005, Pages 309~318
Rhus verniciflua Stokes (RVS) has been used as a food supplement and a traditional herbal medicine. In this study, we prepared various flavonoid fractions (RS, RW1, RW2 and RWE) from a hot water extract of RVS and their influence on male reproductive organs and spermatogenesis were studied in rats which were orally administered 200 mg/kg of them for 8 weeks. All experimental groups did not show any significant changes in body weight and blood clinical chemistry for liver function. Plasma testosterone level was elevated about 3.7, 5.2 and 6.3 folds in RW1, RW2 and RWE groups, respectively. The weights of testes and epididymides tended to increase slightly without the statistical significance in RW2 and RWE. The spermatozoon motility and epididymal sperm concentration were significantly increased (P<0.05) in RWE and RW1, respectively, when compared to the control group. There was no significant difference in histology and apparent shape of testes and epididymides among the control and the experimental groups. Collectively, RWE showed effectively the elevation of plasma testosterone level, spermatozoon motility and the epididymal sperm concentration without the significant increase of testis and epidiymides weights. When the component HPLC profile among the flavonoids fractions of RVS was compared, the ratio of components were only different. These findings suggest that the Rhus flavonoid fraction, particularly RWE, can stimulate the androgen-dependent male sexual function and it can be applied to the material of functional food for enhancing the sexual function.
Systemic Availability and Pharmacokinetics of Surfactin, a Lipopeptide Produced by Bacillus subtilis BC1212 in Rats
Lim Jong-Hwan ; Kim Myoung-Seok ; Park Byung-Kwon ; Hwang Youn-Hwan ; Hwang Mi-Hyun ; Park Seung-Chun ; Yun Hyo-In ;
Toxicological Research, volume 21, issue 4, 2005, Pages 319~323
The aim of the present study was to evaluate systemic bioavailability of surfactin and to determine its pharmacokinetic profiles. The stability of surfactin to pH, temperature and protease was evaluated. Surfactin was resistant to high temperature, a wide range of pH and the action of hydrolytic enzymes. The pharmacokinetic natures of surfactin which were shown the short half-life, rapid clearance and poor bioavailability. The results of study should provide preliminary data of surfactin for further dose-finding studies and for the design of application forms. It is also be important to a context of the safety of surfactin.
Effects of Licorice on Embryonic and Fetal Development in Rats
Shin Sunhee ; Jang Ja Young ; Baek In-Jeoung ; Yon Jung-Min ; Nam Sang-Yoon ; Yun Young Won ; Cho Dae-Hyun ; Kim Soon-Sun ; Rhee Gyu-Seek ; Kwack Seung-Jun ; Kim Yun-Bae ;
Toxicological Research, volume 21, issue 4, 2005, Pages 325~332
The developmental toxicity of water extract of licorice (Glycyrrhiza glabra) was evaluated in rats. Licorice extract (500, 1,000 or 2,000 mg/kg) was dissolved in drinking water and orally administered to male rats from 9 weeks before mating to the day of copulation, and to females from 2 weeks before mating to gestational day 19. On gestational day 20, the animals were sacrificed for Cesarian section, and maternal and fetal abnormalities were examined. Licorice extract neither induce clinical signs, nor affect the body weight gain, feed and water intake, estrous cycle, copulation and fertility rates, blood
level and organ weights of dams. Also, the implantation and development including body weights, absorption and death of embryos and fetuses were not influenced by in utero exposure to licorice. In addition, there were no increases in external, visceral and skeletal abnormalities of fetuses. Taken together, it is suggested that no observed adverse effect level of licorice extract is higher than 2,000 mg/kg, and that long-term in utero exposure to licorice might not cause developmental toxicities of embryos and fetuses.
Thyroid Hormones Receptor/Reporter Gene Transcription Assay for Food Additives and Contaminants
Jeong Sang-Hee ; Cho Joon-Hyoung ;
Toxicological Research, volume 21, issue 4, 2005, Pages 333~338
Many of thyroid hormones disrupting chemicals induce effects via interaction with thyroid hormone and retinoic acid receptors and responsive elements intrinsic in target cells. We studied thyroid hormones disrupting effects of food additives and contaminants including BHA, BHT, ethoxyquin, propionic acid, sorbic acid, benzoic acid, CPM, aflatoxin B1, cadmium chloride, genistein, TCDD, PCBs and TDBE in recombinant HeLa cells containing plasmid construct for thyroxin responsive elements. The limit of response of the recombinant cells to T3 and T4 was
. BHA. genistein, cadmium and TBDE were interacted with thyroid receptors with dose-responsive pattern. In addition, BHA, BHT, ethoxyquin, propionic acid, benzoic acid, sorbic acid, and TBDE showed synergism while cadmium chloride antagonism for T3-induced activity. This study elucidates that recombinant HeLa cell is sensitive and high-throughput system for the detection of chemicals that induce thyroid hormonal disruption via thyroid hormone receptors and responsive elements. Also this study raised suspect of BHA. BHT, ethoxyquin, propionic acid, benzoic acid, sorbic acid, TBDE, genisteine and cadmium chloride as thyroid hormonal system disruptors.
DNA Adduct Formation and Expression of Ras Gene in the Liver of Rats Treated with Aflatoxins at Various Levels
Kim Tae Myoung ; Hue Jin Joo ; Li Lan ; Kim Dae Joong ; Nam Sang Yoon ; Yun Young Won ; Lee Beom Jun ;
Toxicological Research, volume 21, issue 4, 2005, Pages 339~345
Aflatoxins are produced by Aspergillus flavus, parasiticus that grows in improperly stored cereals. Aflatoxin
is a potent hepatocarcinogen in a variety of experimental animals including human beings. In spite of a high attention to the hepatocarcinogenecity of aflatoxins, the relative toxicity of other types
of the toxins is not fully clarified. Sprague-Dawley male rats were orally administered with
at the dose of 250, 1250, and
body weight. Animals were then killed at 12, 24 or 48 hrs following aflatoxin adminstration. Subsequently the relative weight of liver was measured and histopathological examination on the liver was performed. Level of 8-OxodG and expression of ras gene in the liver was determined. The relative liver weights at high doses of
was significantly low. The treatment of
at the high dose of
showed vacuolar degeneration and centrilobular hepatic necrosis with inflammatory cells. The pathological changes by
were not clearly found. The formation of 8-OxodG by
increased in a dose-dependent manner up to 24 hrs after a single treatment of
thereafter decreased to the level of the control. The treatments of
showed an inconsistent pattern in the formation of 8-OxodG in the liver of rats with increasing time. The expression of ras oncogene in the liver by
at the dose of
was increased twice compared to the control. The treatments of
at all doses decreased the expression of ras in the liver. These results in the present study indicate that
among aflatoxins with low comparable levels is the most toxic as determined by early biomarkers such as 8-OxodG formation and ras expression. However, the levels of 8-OxodG and ras as biomarkers were not useful to predict the relative hepatocarcinogenicity of aflatoxins to
in the present model. Further studies are required to look for other biomarkers to predict carcinogenic potency of aflatoxins.
4-(N-Methyl-N-nitrosamino)-1(3-pyridyl)-1-butanone(NNK) Restored the Cap-dependent Protein Translation Blocked by Rapamycin
Kim Jun-Sung ; Park Jin Hong ; Park Sung-Jin ; Kim Hyun Woo ; Hua Jin ; Cho Hyun Sun ; Hwang Soon Kyung ; Chang Seung Hee ; Tehrani Arash Minai ; Cho Myung Haing ;
Toxicological Research, volume 21, issue 4, 2005, Pages 347~353
Eukaryotic initiation factor 4E (elF4E) is a key element for cap-dependent protein translation controlled by affinity between elF4E and 4E-binding protein 1 (4E-BP1). Rapamycin can also affect protein translation by regulating 4E-BP1 phosphorylation. Tobacco-specific nitrosamine, 4(N-methyl-N-nitrosamino )-1-(3-pyridyl)-1-butanone (NNK) is a strong lung carcinogen, but its precise lung cancer induction mechanism remains unknown. Relative roles of cap-dependent and -independent protein translation in terms of NNK-induced lung carcinogenesis were elucidated using normal human bronchial epithelial cells. NNK concentrations applied in this study did not decrease cell viability. Addition of NNK restored rapamycin-induced decrease of protein synthesis and rapamycin-induced phosphorylation of 4E-BP1, and increased expression levels of mTOR, ERK1/2, p70S6K, and Raf-1 in a concentration-dependent manner. NNK also caused perturbation of normal cell cycle progression. Taken together, NNK might cause toxicity through the combination of restoration of 4E-BP1 phosphorylation and increase of elF4E as well as mTOR protein expression, interruption of Raf1/ERK as well as the cyclin G-associated p53 network. Our data could be applied towards elucidation of the molecular basis for lung cancer treatment.
Inhibition of Cell Proliferation and Induction of Apoptosis by Diallyl Disulfide in Human Colon Cancer Cell lines
Kim Tae Myoung ; Ryu Jae Myun ; Kwon Hyun Jung ; Woo Koan Sik ; Jeong Heon Sang ; Hong Jin Tae ; Kim Dae Joong ;
Toxicological Research, volume 21, issue 4, 2005, Pages 355~360
Epidemiological and laboratory studies provide insight into the anti-carcinogenic potential of garlic and its constituent compounds. Garlic is appealing as an anti-carcinogenic agent due to its ability to induce apoptosis in vitro. Diallyl disulfide (DADS) is one of the major components of garlic that used to determine inhibition of cell proliferation and induced apoptosis in human colon cell lines. In this study, human colorectal cancer cell lines (LOVO, HCT-116, SW-480) were exposed to DADS. The inhibitory effects of DADS dose level more than
in the cell viability of all cell lines. Cell growth activity inhibits of human colon cancer cell lines. The inhibitory effects of DADS dose level more than
in the cell growth using MTT assay. We found that DADS may have the apoptosis action (chromatin condensation, DNA fragmentation) using DAPI staining and increased the expression of caspase-3 at the dose level more than
, decreased the expression level of
at dose dependent in the western blotting. We suggest that DADS may have a potential candidate as cancer chemopreventive agents.
Single Oral Dose Toxicity Studies of Polycan, β-Glucan Originated from Aureobasidium in Mice
Lee, Hyeung-Sik ; Yang, Kun-Ju ; Shin, Hyun-Dong ; Park, Bok-Ryeon ; Son, Chang-Woo ; Jang, Hee-Jeong ; Park, Dong-Chan ; Jung, Young-Mi ; Ku, Sae-Kwang ;
Toxicological Research, volume 21, issue 4, 2005, Pages 361~365
This study was conducted to obtain the acute information of the oral dose toxicity of Polycan - originated from Aureobasidium pullulans SM-2001 (half of the dry material is -1,3/1,6-glucans), a UV induced mutant of A. pullulans, having various pharmacological effects, in male and female mice. In order to calculate
, approximate LD and target organs, test article was administered twice by oral gavage to male and female ICR mice at total 1000, 500 and 250mg/kg. The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after dosing. As the results, we could not find any mortalities, clinical signs, changes in the body weight and gross findings. The results obtained in this study suggest that the Polycan is non-toxic in mice and is therefore likely to be safe for clinical use. The L050 and approximate
in mice after single oral dose of Polycan were considered over 1000 mg/kg, respectively.