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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 20, Issue 4 - Sep 2004
Volume 20, Issue 3 - Sep 2004
Volume 20, Issue 2 - Jun 2004
Volume 20, Issue 1 - Mar 2004
Selecting the target year
Importance of Peer Review in Toxicological Pathology and Its Practical Approach
Toxicological Research, volume 20, issue 1, 2004, Pages 1~11
Evaluation of toxicological pathology is to some extend subjective judgments by pathologist and the accuracy of pathologist's works is based on the individual training and experiences. It has been required to establish a peer review system for toxicologic pathology and these review system has been employed by various practice of toxicological pathology. It would be pointed out that the possible causes of drifts in pathology are due to 1) lack of knowledge or experience of individual pathologists, 2) poorly maintained consistence of grading among animals in study, 3) different interpretation of findings between pathologists, or 4) pathology data processing. Example cases of diagnostic errors and current practice of peer review including tissue selection criteria, documentation and problem resolution for short-term and carcinogenicity studies were introduced. For sound regulatory system and high integrity of practice in toxicological pathology, current approaches of peer review system were reviewed.
Comparative Biocompatibility of Metal Implants in Connective Tissue of Abdominal Wall of the Mouse
Toxicological Research, volume 20, issue 1, 2004, Pages 13~20
The purpose of this study is to compare the biocompatibility of commercial purity Ti, Ti-6AI-4V and Ti-6AI-7Nb alloy specimens with and without surface treatment in mouse abdominal connective tissue in vivo. Each metal was implanted into specific abdominal subdermal tissue site of female mouse. After 4 weeks, the implants were removed and abdominal tissues were fixed, dehydrated and embedded in glycol methacrylate resin. And the tissues were histologically prepared for microscopical evaluation. It was characterized by the presence of connective tissue with fibrous capsule surrounding the implant. The fibrous tissue surrounding the implant was studied to determine the biocompatibility of implanted metals. The average thickness of the fibrous capsule formed around the implant was much thinner for the hydrogen peroxide added hydrochloric acid solution-treated specimen than for the others. The results of this evaluation indicate that modification of the surface properties of titanium and titanium alloy implants changes the biological properties in the abdominal connective tissue. In conclusion, these observations suggest that the proper surface treatment performed in the study is effective for the improvement of biocompatibility.
The mRNA Expression of Radio-Sensitive Genes Exposed to Various Dosage of Ionizing Radiation in U-937 Cell
Toxicological Research, volume 20, issue 1, 2004, Pages 21~29
We used cDNA microarray to assess gene expression profiles in hematopoetic cell line, U-937, exposed to low doses of ionizing irradiation. The 1,000 DNA elements on this array were PCR-amplified cDNAs selected from named human cancer related genes. According to the strength of irradiation, the levels of some gene expression were increased or decreased as dose-dependent manner. The gene expressions of Tubulin alpha, protein kinase, interferon-alpha, -beta, -omega receptor and ras homolog gene family H were significantly increased. Especially, Tubulin gene was shown 2.5 fold up-regulated manner under stress of 500 rad irradiation than 200 rad. On the other hand, fibroblast growth factor 12 and four and a half LIM domains, etc. were significantly down-regu-lated. Also, tumor protein 53(TP53) related genes that p53 inducible protein, tumor protein 53-binding protein looks of little significance as radiation sensitive manner. The radio-sensitivity of tubulin gene etc. that we proposed could be useful to rapid and correct survey for the bio-damage by exposure to low dose irradiation.
Effect of Radiation on mRNA Expression of Ceruloplasmin Gene
Toxicological Research, volume 20, issue 1, 2004, Pages 31~36
Against environmental stress, ceruloplasmin which is a plasma protein, are believed to play central roles in antioxidant- or peroxidase-activity in blood stream to remove free radicals, which may be caused by exposing of
-irradiation. In human U-937 cells exposed to
-irradiation, the levels of mRNA in ceruloplasmin gene were measured on 0, 4, 12, 24 hr after exposing by using comparative RT-PCR (Reverse transcriptase-polymerase chain reaction) which was achieved to compare with house keeping genes such as
-actin and hprt. After
-irradiation of 100 rads or 200 rads, the total quantities of RNA were increased as dose and time dependent manner. On the contrary, the variation of mRNA expression in ceruloplasmin was not found until 4 hr after irradiation. After 12 hr and 24 hr of irradiation, the levels of mRNA in ceruloplasmin were significantly increased as dose and time dependent manner than un-exposed cells.
Comparative Antitumor Activity of Water Extracts from Fruiting Body of Phellinus linteus, Phellinus baumii and Phellinus gilvus
Toxicological Research, volume 20, issue 1, 2004, Pages 37~42
This study was undertaken to investigate comparative anti-tumor activity of water extracts of Phellinus gilvus (PGE), Phellinus linteus (PLE), and Phellinus baumii (PBE) in vitro. The anti-tumor activity in the present study was evaluated by sulforhodamine B (SRB) and microtetrazolium (MTT) assay in terms of cell survival level. The tumor cells (sarcoma 180 and P388) were treated with PGE, PLE, and PBE (7.5, 15, and 30
/ml) and Doxorubicin (DOX) (0.001~10
). The results showed that DOX, PGE, and PLE inhibited proliferation showing a dose-dependent manner against both tumor cells. However, PBE was inhibited by the only 30
/ml in both cells proliferation. In conclusion, all of PGE, PLE, and PBE used in this study have shown anti-tumor activity against both sarcoma 180 and P388. Among them, PLE was the most effective in anti-tumor activity against sarcoma 180 (p<0.05) and PGE was against P388 in SRB assay. PLE, however, was against P388 (p<0.05) in MTT assay.
Genotoxicity Study of Water Extract of Anemarrhena asphodeloides and Phellodendron amurense in Bacterial and Mammalian Cell Systems
Chung, Young-Shin ; Lee, Seok-Jong ; Choi, Sun-A ; Lee, Jang-Ha ; Ryu, Jae-Chun ; Hong, Eun-Kyung ;
Toxicological Research, volume 20, issue 1, 2004, Pages 43~47
In order to investigate the safety of a water extract (ADP) of 1 : 1 mixture of Anemarrhena rhizoma and Phellodendron cortex for alleviating benign prostate hyperplasia, genotoxicity studies in bacterial and mammalian cell assay systems, namely, the Ames bacterial reverse mutation and chromosomal aberration assays were performed. As shown by the results of the Ames bacterial reversion assay, ADP in the range of 625-5000
/plate did not induce mutagenicity in Salmonella typhimurium TA 98, TA 100, TA 1535 and TA 1537 strains in the absence or in the presence of S9 (the microsomal fraction of rat liver homogenate) metabolic activation. The
(50% cell growth inhibition concentration) values of ADP for the chromosomal aberration assay were determined; these were 2425
/ml in the absence and 8126
/ml in the presence of S9 metabolic activation in Chinese hamster lung (CHL) fibroblast cell culture. No chromosomal aberration was observed in CHL cells treated with ADP at 2425, 1212.5 and 606.25
/ml in the absence, or at 8126, 4063 and 2031.5
/ml in the presence of S9 metabolic activation. These results show that under the conditions used, ADP does not harmfully affect the bacterial or mammalian cell system at the gene level.
Linkage Disequilibrium of Dopamine D2 Receptor Gene in the Korean Population
Kang, Byung-Yong ; Oh, Sang-Duk ; Lee, Kang-Oh ;
Toxicological Research, volume 20, issue 1, 2004, Pages 49~53
The genetic basis of hypertension is complex, and has been considered to be associated with the dopamine D2 receptor gene (DD2R). Because association studies using the candidate gene approach may provide important clues regarding the pathogenesis of hypertension and establish basis for further study, we performed the association study on the relationship between genetic polymorphisms in the DD2R gene and hypertension in Koreans. Eighty nine patients with hypertension and 86 age-matched subjects with normal blood pressure were enrolled. Genomic DNA was extracted from peripheral blood leukocytes. PCR-RFLP analysis was performed to detect the three polymorphic Taq I sites in the DD2R gene. There were no significant differences in genotype, allele and haplotype distributions of any polymorphisms in the DD2R gene between two groups, respectively (P>0.05), although significant linkage disequilibriums among these polymorphic sites were detected by pair-wise analysis (P<0.05). Therefore, our negative result suggest that the three Taq I RFLPs in the DD2R gene were not significantly associated with hypertension in Koreans.
Changes of Pulmonary Function!) During 60 days of Welding Fume Exposure Period 1m Sprague-Dawley Rats
Toxicological Research, volume 20, issue 1, 2004, Pages 55~61
Respiratory effects in full time welders include bronchitis, airway irritation, lung function changes, and lung fibrosis. Welder's pneumoconiosis has been generally determined to be benign and not associated with respiratory symptoms based on the absence of pulmonary function abnormalities in welders with marked radiographic abnormalities. Accordingly, to investigate pulmonary function changes during 60 days induced by welding-fume exposure, male Sprague-Dawley rats were exposed to manual metal arc-stainless steel (MMA-SS) welding fumes with concentrations of 64.8
(low dose) and 107.8
(high dose) total suspended particulates for 2 hr/day, 5 days/week in an inhalation chamber for 60 days. Pulmonary function was measured every week with whole body plethysmograph compensated (WBP Comp, SFT38116, Buxco Electronics, Sharon, CT). The rats exposed to the high dose of welding fumes exhibited statistically significant (p<0.05~0.01) body weight decrease as compared to the control whereas cell number increase of the bronchoalveolar lavage fluid (BALF) (total cell, macrophage, polymorphonuclear cell and lymphocyte) during the 60 days exposure period. And only tidal volume was significantly decreased in dosedependantly during 60 days of MMA-SS welding fume exposure. This pulmonary function change with inflammatory cell recruitment confirms the lung injury caused by the MMA-SS welding fume exposure.
Protective Effects of Chitosan on the Cadmium Cytotoxicity in Rat Glioma Cells
Toxicological Research, volume 20, issue 1, 2004, Pages 63~69
Casapse-3 protease is known as a key role of apoptotic enzyme, and caspase-3 activity is a central event that occurs upstream of DNA fragmentation during apoptosis. This study demonstrates that chitosan pretreatment inhibits cadmium-induced apoptosis by attenuating the activity of caspase-3. We also analyzed the protective effect of chitosan on DNA fragmentation induced by cadmium. Cadmium toxicity was examined by DNA fragmentation and nuclear condensation with Hoechst stain. Caspase-3 activities were increased cadmium treated group for 3 hours compared with control. When chitosan (150 mg/ml) was pretreated at 30 min before cadmium treatment, cadmium cytotoxicity was suppressed in a dose-dependent manner evaluated by DNA fragmentation and caspase activity. From these results, it is suggest that the protective effect of chitosan pretreatment against cadmium-induced cytotoxicity is mediated through inhibition of caspase-3 protease activation and DNA fragmentation.
Ozone Inhalation with 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)- 1-butanone and/or Dibutyl Phthalate Induced Cell Cycle Alterations via Wild-type p53 Instability in B6C3F1 Mice
Kim, Min-Young ; Song, Kyung-Suk ; Park, Gun-Ho ; Kim, Hyun-Woo ; Park, Jin-Hong ; Kim, Jun-Sung ; Jin, Hwa ; Kook-Jong, Eu ; Cho, Hyun-Sun ;
Toxicological Research, volume 20, issue 1, 2004, Pages 71~82
Changes in cell cycle control in the lungs and liver of the B6C3F1 mice (20 males per each group) exposed to ozone (0.5 ppm), 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 1.0 mg/kg), and dibutyl phthalate (DBP, 5,000 ppm) after 52 weeks were examined through Western, Northern blot, and immunohistochemistry based on alterations in protein expression levels of G1/S checkpoints (cyclin D1, cyclin E, and PCNA), G2/M checkpoints (cyclin B1, cyclin G, and cyclin A), negative regulators (p53, p21, GADD45, and p27), and positive regulator (mdm2). Expression levels of cyclins D1, E, G, PCNA, mutant p53, and mdm2 proteins were higher in the lungs and livers treated with combination of toxicants than in those treated with ozone only. Expression levels of the wild-type and mutant p53, p21, GADD45, p27, and mdm2 proteins and mRNAs were higher in toxicant-treated groups than those of the control. Immunohistochemical analysis revealed staining intensities of the PCNA, cyclin D1, c-myc and mdm2 protein- treated lungs and livers were stronger than those of the control group. Our results showed that combined treatment of ozone with NNK/DBP altered the cell cycle control through instability of the wild-type p53 gene. Such pivotal p53-mediated cell cycle alterations may be responsible for the toxicity observed under our experimental condition. These results may be applied to risk assessment of mixture-induced toxicity.
5-Day Repeated Intravenous Dose Toxicity Study of a New Camptothecin Anticancer Agent CKD-602 in Rats
Kim, Jong-Choon ; Shin, Dong-Ho ; Kim, Sung-Ho ; Bae, Chun-Sik ; Kim, Joon-Kyum ; Cha, Shin-Woo ; Han, Jung-Hee ; Lee, Hyun-Sook ; Chung, Moon-Koo ;
Toxicological Research, volume 20, issue 1, 2004, Pages 83~88
The present study was carried out to investigate the potential adverse effects of CKD-602 by a 5-day repeated intravenous dose in Sprague-Dawley rats. The test article, CKD-602, was administered intravenously to male and female rats at dose levels of 0.07, 0.22, 0.67, 2.0 and 6.0 mg/kg/day for 5 days consecutively. Mortalities, clinical findings, and body weight changes were monitored for the 14-day period after cessation of the administration. At the end of 14-day observation period, all animals were sacrificed and complete gross postmortem examinations were performed. There were 2 and 5 treatment related deaths in the 0.67 and 2.0 mg/kg/day dose groups of both genders, respectively. Treatment related clinical signs, including hair loss, skin paleness, decreased locomotor activity, emaciation, and changes in stool were observed in a dose-dependent manner from the third day after initiation of the injection. Decrease or suppression of body weight was also observed dose-dependently in males and females of the treated groups. Gross postmortem examinations revealed a dose-dependent increase in the incidence and severity of atrophy or hypertrophy and white membrane formation in the spleen, atrophy of the thymus, diffuse white spots and paleness of the liver, paleness of the lung, kidney and adrenal gland, and dark red discoloration and dark red contents in the alimentary tract. Based on these results, it was concluded that the 5-repeated intravenous injection of CKD-602 to male and female rats resulted in increased incidence of abnormal clinical signs and death, decreased or suppressed body weight, and increased incidence of abnormal gross findings. In the present experimental conditions, the
value was 2.07 (95% confidence limit not specified) mg/kg/day in both genders and the
value was 1.72 (95% confidence limit not specified) mg/kg/day in both genders.