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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 27, Issue 4 - Dec 2011
Volume 27, Issue 3 - Sep 2011
Volume 27, Issue 2 - Jun 2011
Volume 27, Issue 1 - Mar 2011
Selecting the target year
Developing Korean Standard for Nanomaterial Exposure Assessment
Lee, Ji-Hyun ; Lee, Jun-Yeob ; Yu, Il-Je ;
Toxicological Research, volume 27, issue 2, 2011, Pages 53~60
DOI : 10.5487/TR.2011.27.2.053
Nanotechnology is now applied to many industries, resulting in wide range of nanomaterial-containing products, such as electronic components, cosmetic, medicines, vehicles, and home appliances. Nanoparticles can be released throughout the life cycle of nanoproducts, including the manufacture, consumer use, and disposal, thereby involving workers, consumers, and the environment in potential exposure. However, there is no current consensus on the best sampling method for characterizing manufactured-nanoparticle exposure. Therefore, this report aims to provide a standard method for assessing nanoparticle exposure, including the identification of nanoparticle emission, the assessment of worker exposure, and the evaluation of exposure mitigation actions in nanomaterial-handling workplaces or research institutes.
Molecular Mechanism of Tetrabromobisphenol A (TBBPA)-induced Target Organ Toxicity in Sprague-Dawley Male Rats
Choi, Jae-Seok ; Lee, Young-Jun ; Kim, Tae-Hyung ; Lim, Hyun-Jung ; Ahn, Mee-Young ; Kwack, Seung-Jun ; Kang, Tae-Seok ; Park, Kui-Lea ; Lee, Jae-Won ; Kim, Nam-Deuk ; Jeong, Tae-Cheon ; Kim, Sang-Geum ; Jeong, Hye-Gwang ; Lee, Byung-Mu ; Kim, Hyung-Sik ;
Toxicological Research, volume 27, issue 2, 2011, Pages 61~70
DOI : 10.5487/TR.2011.27.2.061
Brominated flame retardants (BFRs) are present in many consumer products ranging from fabrics to plastics and electronics. Wide use of flame retardants can pose an environmental hazard, which makes it important to determine the mechanism of their toxicity. In the present study, dose-dependent toxicity of tetrabromobisphenol A (TBBPA), a flame retardant, was examined in male prepubertal rats (postnatal day 18) treated orally with TBBPA at 0, 125, 250 or 500 mg/kg for 30 days. There were no differences in body weight gain between the control and TBBPA-treated groups. However, absolute and relative liver weights were significantly increased in high dose of TBBPA-treated groups. TBBPA treatment led to significant induction of CYP2B1 and constitutive androstane receptor (CAR) expression in the liver. In addition, serum thyroxin (T4) concentration was significantly reduced in the TBBPA treated group. These results indicate that repeated exposure to TBBPA induces drug-metabolising enzymes in rats through the CAR signaling pathway. In particular, TBBPA efficiently produced reactive oxygen species (ROS) through CYP2B1 induction in rats. We measured 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidative damage, in the kidney, liver and testes of rats following TBBPA treatment. As expected, TBBPA strongly induced the production of 8-OHdG in the testis and kidney. These observations suggest that TBBPA-induced target organ toxicity may be due to ROS produced by metabolism of TBBPA in Sprague-Dawley rats.
Inhibition of p65 Nuclear Translocation by Baicalein
Seo, Min-Bum ; Lee, Seog-Ki ; Jeon, Young-Jin ; Im, Jin-Su ;
Toxicological Research, volume 27, issue 2, 2011, Pages 71~76
DOI : 10.5487/TR.2011.27.2.071
We demonstrate that baicalein, a bioactive flavonoid originally isolated from Scutellaria baicalensis, inhibits LPS-induced expression of iNOS gene in RAW 264.7 cells. Treatment of peritoneal macrophages and RAW 264.7 cells with baicalein inhibited LPS-stimulated nitric oxide production in a dose-related manner. Immunohistochemical staining 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. Immunostaining of p65, EMSA, and reporter gene assay showed that baicalein inhibited NF-
B nuclear translocation, DNA binding, and transcriptional activation, respectively. Collectively, these series of experiments indicate that baicalein inhibits iNOS gene expression by blocking NF-
B nuclear translocation. Due to the critical role that NO release plays in mediating inflammatory responses, the inhibitory effects of baicalein on iNOS suggest that baicalein may represent a useful anti-inflammatory agent.
Comparative Antitumor Activity of Different Solvent Fractions from an Auricularia auricula-judae Ethanol Extract in P388D1 and Sarcoma 180 Cells
Reza, Ahsanur ; Choi, Myung-Jin ; Damte, Dereje ; Jo, Woo-Sik ; Lee, Seung-Jin ; Lee, Joong-Su ; Park, Seung-Chun ;
Toxicological Research, volume 27, issue 2, 2011, Pages 77~83
DOI : 10.5487/TR.2011.27.2.077
The objective of this study was to evaluate and compare the antitumor activity of different solvent fractions (ethanol, dichloromethane, ethyl acetate, butanol and water) of the Auricularia auricula-judae 70% ethanol extract on the P388D1 macrophage and sarcoma 180 cells. A dose-dependent antitumor activity of each solvent fraction (from 0.01 mg/ml to 0.3 mg/ml) was shown against both cell types. These cytotoxic effects of all the tested fractions were confirmed on the MTT and SRB assays, without statistical differences each other.
value of dichloromethane fraction was 94.2
against sarcoma 180 cells lower than any other solvent fractions. The potent antitumor effect of the dichloromethane (DCM) fraction was also found against solid tumor in BALB/c mice. The splenomegaly and higher splenic index were found in tumor-bearing mice, with the DCM fraction returning to the negative control values. Thus, the results indicated the dichloromethane fraction may have potential ingredients as antitumor candidates.
The Effect of Selective Estrogen Receptor Modulators (SERMs) on the Tamoxifen Resistant Breast Cancer Cells
Chang, Bo-Yoon ; Kim, Sae-Am ; Malla, Bindu ; Kim, Sung-Yeon ;
Toxicological Research, volume 27, issue 2, 2011, Pages 85~93
DOI : 10.5487/TR.2011.27.2.085
Selective estrogen receptor modulators (SERMs) are synthetic molecules which bind to estrogen receptors (ER) and can modulate its transcriptional capabilities in different ways in diverse estrogen target tissues. Tamoxifen, the prototypical SERM, is extensively used for targeted therapy of ER positive breast cancers. Unfortunately, the use of tamoxifen is associated with acquired resistance and some undesirable side effects. This study investigated the availability of the conventional SERMs on the TAM-resistance breast cancer cells. SERMs showed more effectiveness in MCF-7 cells than tamoxifen resistant cells, except toremifene and ospemifene. Especially, toremifene was more efficacious in tamoxifen resistant cells than MCF-7. Ospemifene had similar cytotoxic activity on the two types of breast cancers. The other SERMs used in this experiment didn't inhibit efficiently the proliferation of tamoxifen resistant cells. These results support the possibility to usage of toremifene on tamoxifen resistant cancer. The effectiveness by toremifene on tamoxifen resistant cells might be different pathways from the apoptosis and the autophagy. Further study should be needed to elucidate the underlying mechanism of effect of toremifene on tamoxifen resistant cancer.
Effect of DHU001, a Polyherbal Formula on Formalin-induced Paw Chronic Inflammation of Mice
Cho, Yoon-Hee ; Chung, In-Kwon ; Cheon, Woo-Hyun ; Lee, Hyeung-Sik ; Ku, Sae-Kwang ;
Toxicological Research, volume 27, issue 2, 2011, Pages 95~102
DOI : 10.5487/TR.2011.27.2.095
The effect of DHU001, a mixed herbal formula consisted of 7 types aqueous extracts for various respiratory disorders were evaluated on the formalin-induced paw chronic inflammation in mice after oral administration. Mice were subaponeurotically injected in the left hind paw with 0.02 ml of 3.75% formalin, then subjected to 500, 250 and 125 mg/kg of DHU001 oral administration, once a day for 10 days during which then the hind-paw thickness and volume were measured daily. The paw wet-weight, histological profiles, histomorphometrical analyses and paw tumor necrosis factor (TNF)-
contents were conducted at termination. After two formalin treatments, a marked increase in the paw thickness and volume was detected in the formalin-injected control as compared with that in the intact control, plus at the time of sacrifice the paw wet-weights, paw TNF-
contents were also dramatically increased with severe chronic inflammation signs at histopathological observations. However, these formalin-induced chronic inflammatory changes were dramatically decreased by treatment of dexamethasone and all three different dosages of DHU001. DHU001 has favorable effects on formalin-induced chronic inflammation mediated by TNF-
suppression, and DHU001 may represent an alternative approach for the treatment of chronic inflammatory diseases.
Lipotoxicity of Palmitic Acid on Neural Progenitor Cells and Hippocampal Neurogenesis
Park, Hee-Ra ; Kim, Ji-Young ; Park, Kun-Young ; Lee, Jae-Won ;
Toxicological Research, volume 27, issue 2, 2011, Pages 103~110
DOI : 10.5487/TR.2011.27.2.103
Lipotoxicity involves pathological alterations to cells and tissues in response to elevated fat levels in blood. Furthermore, this process can disturb both cellular homeostasis and viability. In the current study, the authors show that neural progenitor cells (NPCs) are vulnerable to high levels of palmitic acid (PA) a saturated fatty acid. PA was found to cause cell death associated with elevated reactive oxygen species (ROS) levels, and to reduce NPCs proliferation. To evaluate the lipotoxicity of PA in adult NPCs in the hippocampus, male C57BL/6 mice were divided into two groups and maintained on either a normal diet (ND) or PA-rich high fat diet (HFD) for 2 weeks. Interestingly, short-term PA-rich HFD feeding reduced the survival of newly generated cells in the hippocampal dentate gyrus and hippocampal brain-derived neurotrophic factor levels. These findings suggest PA has a potent lipotoxicity in NPCs and that a PA-rich HFD disrupts hippocampal neurogenesis.
Toxicity Study of Streptococcus pneumoniae Vaccine Administrated Subcutaneously in Rats
Park, Sin-Jeong ; Seo, Kook-Heon ; Han, Sang-In ;
Toxicological Research, volume 27, issue 2, 2011, Pages 111~118
DOI : 10.5487/TR.2011.27.2.111
This study was performed to evaluate the toxicity of polysaccharide-based Streptococcus pneumoniae vaccine in Specific Pathogen Free (SPF), Sprague-Dawley (SD) rats. S. pneumoniae vaccine was administrated subcutaneously each dose level of high (560
/rat), medium (280
/rat) and low (140
/rat) on days 0, 14, 28. The rats were observed for 2 weeks or 4 weeks after the final injection. During this test, there were no significant dose-dependent changes in body weight, water and food consumption. In urinalysis and serum chemistry, dose-related changes were not detected. In hematology, the percent of neutrophils and lymphocytes in white blood cells were changed significantly. According to the measurement of organ weight, only spleen weight was significantly increased in all groups of administration compared to the control group. In the histopathological examination, an antigen-deposit, vacuolated macrophages, infiltrated inflammatory cells and a formation of granulation tissue were observed at the site of an administration. These results are considered as an outcome by immune responses through a vaccination. Consequently, the results of this study demonstrated that S. pneumoniae vaccine has no toxicity when it was administrated subcutaneously three times in 2-week interval at a high dose of 560
Micronucleus Test of Picrorrhiza Rhizoma Aqueous Extract in Bone Marrow Cells of Male ICR Mice
Chung, In-Kwon ; Cheon, Woo-Hyun ; Ku, Sae-Kwang ;
Toxicological Research, volume 27, issue 2, 2011, Pages 119~123
DOI : 10.5487/TR.2011.27.2.119
In this research, the genotoxic effect of Picrorrhiza Rhizoma (PR) aqueous extract was evaluated using the mouse micronucleus test. PR extract was administered once a day for 2 continuous days by oral gavage to male ICR mice at doses of 2000, 1000 and 500 mg/kg. Cyclophosphamide was used as a known genotoxic agent in a positive control. The appearance of a micronucleus (MN) in polychromatic erythrocyte (PCE) is used as an index for genotoxic potential, and PCE ratio is used as an index of cytotoxicity. Although significant (p < 0.01) increase of the number of PCE with one or more nuclei (MNPCE) was detected in cyclophosphamide treated groups, no significant increases of MNPCE numbers were observed in all three different dosages of PR extracts treated mice with over 0.39 of the individual polychromatic erythrocyte ratio in all mice used in this study. The results obtained indicated that PR extract shows no genotoxicity effects up to 2000 mg/kg dosing levels.
Production of Group Specific Monoclonal Antibody to Aflatoxins and its Application to Enzyme-linked Immunosorbent Assay
Kim, Sung-Hee ; Cha, Sang-Ho ; Karyn, Bischoff ; Park, Sung-Won ; Son, Seong-Wan ; Kang, Hwan-Goo ;
Toxicological Research, volume 27, issue 2, 2011, Pages 125~131
DOI : 10.5487/TR.2011.27.2.125
Through the present study, we produced a monoclonal antibody against aflatoxin B1 (AFB1) using AFB1-carboxymethoxylamine BSA conjugates. One clone showing high binding ability was selected and it was applied to develop a direct competitive ELISA system. The epitope densities of AFB1-CMO against BSA and KLH were about 1 : 6 and 1 : 545, respectively. The monoclonal antibody (mAb) from cloned hybridoma cell was the IgG1 subclass with
-type light chains. The
of the monoclonal antibody developed for AFB1, AFB2, AFG1 and AFG2 were 4.36, 7.22, 6.61 and 29.41 ng/ml, respectively, based on the AFB1-KLH coated ELISA system and 15.28, 26.62, 32.75 and 56.67 ng/ml, respectively, based on the mAb coated ELISA. Cross-relativities of mAb to AFB1 for AFB2, AFG1 and AFG2 were 60.47, 65.97 and 14.83% in the AFB1-KLH coated ELISA, and 59.41, 46.66 and 26.97% in the mAb coated ELISA, respectively. Quantitative calculations for AFB1 from the AFB1-Ab ELISA and AFB1-Ag ELISA ranged from 0.25 to 25 ng/ml (
> 0.99) and from 1 to 100 ng/ml (
> 0.99), respectively. The intra- and inter-assay precision CVs were < 10% in both ELISA assay, representing good reproducibility of developed assay. Recoveries ranged from 79.18 to 91.27%, CVs ranged from 3.21 to 7.97% after spiking AFB1 at concentrations ranging from 5 to 50 ng/ml and following by extraction with 70% methanol solution in the Ab-coated ELISA. In conclusion, we produced a group specific mAb against aflatoxins and developed two direct competitive ELISAs for the detection of AFB1 in feeds based on a monoclonal antibody developed.