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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 19, Issue 4 - Dec 2003
Volume 19, Issue 3 - Sep 2003
Volume 19, Issue 2 - Jun 2003
Volume 19, Issue 1 - Mar 2003
Selecting the target year
Risk Assessment of Genetically Modified Organisms
Toxicological Research, volume 19, issue 1, 2003, Pages 1~12
New breeding method by genetic engineering is expected as a key technology to solve food shortage due to the growing world population in the year 2000s. Many genetically modified organisms (GMOs) were already developed and the commercial cultivation had started. The first GMO, Flavr Savr tomato, which rotted at a much slower pace than ordinary ones, was developed in US in 1994. Since then, over than 70 different agricultural products including corn, cotton, soybean, papaya, potato, and squash made with genetically modified plants are reportedly on sale worldwide. Supporters favor the GMOs because they have greater yields, longer shelf lives and stronger resistance to disease and insects. On the other hand, opponents say that the supporters ignore a potential danger that they may damage the environment as well as human beings. To assure the safe development and use of GMOs as food and other biotech products, the possible risks on biological environment and human health should be throughly examined and regulated by developer and government. Because the biosafety problem is a global, environmental, and trade issue, a new international treaty is under development. The Cartagena Protocol on Biosafety was adopted at the 1 st Extraordinary Conference of Parties of the Convention on Biological Diversity which was held at Mont-real, Canada, Jan. 29th, 2000. The adoption of the Protocol is seen as a breakthrough in that it is based on the" Precautionary Principle" despite scientific uncertainties surrounding potential risks that GMOs may inflict on human health and the environment and that it has laid the ground for introduction of specific steps to handle international trading of GMOs. In this paper, the authors would like to introduce the current status and perspective of environmental and human risk assessment of GMOs.t of GMOs.
Gene Expression of GX-12, a New Naked DNA Vaccine for HIV Infection, in Reproductive Organs
Park, Seul-Min ; Kang, Kyung-Koo ; Lee, Dong-Sup ; Park, Jae-Hoon ; Sohn, Yong-Sung ; Kim, Chae-Young ; Kim, Byung-Moon ; Kim, Won-Bae ;
Toxicological Research, volume 19, issue 1, 2003, Pages 13~19
GX-12 is a naked DNA vaccine developed by the DongA Pharmaceutical Co. Ltd. and Genexine for the treatment of HIV infection. This study was peformed to evaluate the biodistribution and expression of GX-12 mRNA in gonadal tissues, and to investigate the histopathological changes after the repeated intramuscular injection. GX-12 (400
/head) was injected into the left anterior tibialis once a week for four weeks. On day 1, 5, 15, 30 and 45 after the final administration, gonadal tissues (testes, epididymis, seminal vesicles, penis, prostate glands, ovaries, vagina, uterus) and the injection site (muscle) were harvested and examined for the expression of mRNA by RT-PCR. In addition, histopathological examination was peformed at each time point. At the injection site, mRNA expression of GX-12 was detected only at early time points (1 ~ 15 days after injection) but not thereafter. However, in gonadal tissues, mRNA expression was not identified at all time points both in male and female rats. There were no histopathological changes in all reproductive organs and muscle. Based on these results, it is unlikely that the plasmid DNAs of GX-12 was distributed to- and expressed in gonadal tissues, suggesting that the chance of germline integration and transmission is negligible.
A Teratogenicity Study on Dimethyl Dimethoxy Biphenylate Derivative (DDB-S) in Rats
Toxicological Research, volume 19, issue 1, 2003, Pages 21~27
A teratogenic study of dimethyl dimethoxy biphenylate derivative (DDB-S) was carried out on Sprague-Dawley rats. DDB-S dissolved in saline was administered to male and female rats by intravenously injection at daily doses of 50 mg/kg, 75 mg/kg, and 100 mg/kg. A half of dams were sacrificed at 20th day of gestation to scrutinize the pregnant performances and fetal development. And the remaining dams were allowed to deliver. The growth, reflex, behaviour and reproductive function of F1 offsprings were examined. There was no treatment-related difference in body weight, food consumption and necropsy findings of dams. No gross, skeletal and visceral abnormalities was observed in F1 fetuses from dams treated with DDB-S. F1 offsprings did not show any treatment-related difference in growth, reflex, behaviour and reproductive performance. At caesarean section of F1 dams, no growth retardation and gross abnormality was observed in F2 fetuses. In conclusion, DDB-S did not show any potential teratogenic effect in rats.
No Association of the Human Y Chromosome with Blood Pressure in Korean Male Population
Kang, Byung-Yong ; Kim, Seon-Jeong ; Lee, Kang-Oh ;
Toxicological Research, volume 19, issue 1, 2003, Pages 29~31
It has been reported that the genetic variations in the Y chromosome has influence the blood pressure in some Caucasian male populations, but the effect in non-Caucasian population is unclear. In the present study, we examined the relationship between blood pressure and a HindIII RFLP of Y chromosome in 152 unrelated male individuals of ethnically homogeneous Korean origin. There were no significant differences in systolic and diastolic blood pressures between genotype groups, respectively. However, the frequency of A genotype in Korean population was much higher than those of Caucasian populations (P＜0.05). Therefore, the results of this study will con-tribute the better understanding the genetic characteristics of Y chromosome in Korean population.
Anti-inflammatory Effects of Asiaticoside on Inducible Nitric Oxide Synthase and Cyclooxygenase-2 in RAW 264.7 Cell Line
Toxicological Research, volume 19, issue 1, 2003, Pages 33~37
Asiaticoside has been tested for the ability as an anti-inflammatory drug using lipopolysaccharide (LPS)-stimulated macrophage cell line (RAW 264.7 cell). LPS treatment induced dramatically inducible nitric oxide synthase (iNOS) in RAW cells. However, asiaticoside inhibited LPS-stimulated iNOS induction in a concentration-dependent manner. Especially, higher concentrations (＞50
) of asiaticoside completely blocked iNOS induction. In addition, LPS-stimulated expression of inducible cyclooxygenase (COX-2) and interleukin-1
) was inhibited by asiaticoside treatment. Asiaticoside up to 50
still required to inhibit COX-2 and IL-1
induced by LPS. Consistent with these findings, treatment with asiaticoside suppressed do novo synthesis and cellular accumulation of prostaglandin
to a lesser extent, suggesting that asiaticoside blocked the induction as well as the activity of COX-2 These results suggest the possibility that asiaticoside may be effective therapeutic agents for septic shock and other inflammatory diseases.
Eye Irritation, Skin Irritation and Skin Sensitization Tests for Nonspecific Immunostimulator BARODON
;;;;;;Nguyen Ba Tiep;;;
Toxicological Research, volume 19, issue 1, 2003, Pages 39~44
Two local irritation and skin sensitization studies of nonspecific immunostimulator,
were carried out with New Zealand White rabbits and Hartley guinea pigs. In skin irritation test of male New Zealand White rabbits, body weights were not significantly changed and there were no responses after treatment for 24 or 72 hours and the Primary irritation index (P.1.1.) was '0'. And, in the eye irritation test, there were chemosis in some of rabbits. One of 3 rabbits in washing group was detected chemosis after 24 and 72 h following treatment and 2 of 6 rabbits in non-washing group were detected chemosis after 24h and 7 days following treatment. Therefore, total score is '4' after 24 h and '2' after 72 h following treatment by conforming article "some blood vessel are clearly hyperemic" . However evaluation value is non-irritant because M.O.I. (Mean ocular irritation index) score is below during the all experimental period and no significance through individuals and exposure time. In skin sensitization, the score of skin reaction was graded 1 with 0% sensitization rate. Taken together, these results indicate that
may be non-irritant material. material.
Selective Cytotoxicities of Phenolic Acids in Cancer Cells
Toxicological Research, volume 19, issue 1, 2003, Pages 45~50
The purpose of this study was to determine the role of substituted groups in phenolic compounds to develop an anticancer agent having strong cytotoxicity against cancer cells but weak against normal cells. The phenolic compounds used in this study were gallic acid and ferulic acid with hydroxyl and carboxyl groups, syringic acid with hydroxyl, carboxyl and methoxy groups, and pyre-gallol with hydroxyl groups. Cytotoxicities of these compounds were evaluated by MTT assay for cell viability and XTT assay for cell adhesion activity in normal human skin fibroblast (Detroit 551) and human skin melanoma (SK-MEL-3) cells. Syringic acid, gallic acid and ferulic acid decreased the cell viability and cell adhesion activity in SK-MEL-3 cells but not in Detroit 551 cells while pyrogallol decreased in both cells. The susceptibility of cell viability based on the
values of MTT assay in Detroit 551 cells was in the following order: pyrogallol > gallic acid > ferulic acid > syringic acid, while it was in SK-MEL-3 cells: Syringic acid > progallol > ferulic acid > gallic acid. These results suggest that carboxyl and methoxy groups of these compounds play an important role in selectivity of cytotoxicity in normal and cancer cells.
Single and Four-Week Subcutaneous Toxicity Studies of a Bee Venom Extracts (F1, F3) In Rats
Toxicological Research, volume 19, issue 1, 2003, Pages 51~66
This study was performed to evaluate single and repeated-dose toxicities of Bee Venom Extracts (F1, F3) in Spraque-Dawley. F1 was injected subcutaneously to rat at dose levels of 0, 0.0002, 0.002, 0.02 mg/kg/day for single-dose toxicity study and repeated-dose toxicity study. F3 was injected subcutaneously to rat at dose level of 0, 0.003, 0.03, 0.3 mg/kg/day for single-dose toxicity study and repeated-dose toxicity study. In both studies, there were no dose related changes in mortality, clinical sign, body weight change, food and water consumption, opthalmoscopy, organ weights, urine analysis, biochemical examination, and hematological findings of all animals treated with Bee Venom (F1, F3). Gross and histopathological findings revealed no evidence of specific toxicity related to Bee Venom (F1, F3). These results suggest that the subcutaneous NOEL (No Observed Effect Level) of Bee Venom (F1, F3) may be over F1 -0.02 mg/kg, F3-0.3 mg/kg.
Toxic Bile Salts-Induced Apoptosis of Hepatocytes in Biliary Obstruction Involves Fas-independent Pathway
Oh, Seon-Hee ; Lee, Byung-Hoon ;
Toxicological Research, volume 19, issue 1, 2003, Pages 67~72
Cholestatic liver injury results from the accumulation of toxic bile salts within the liver. The aim of the present study is to elucidate the changes in expression and cellular localization of apoptosis related proteins in the liver of bile duct-ligated (BDL) rat. Extrahepatic cholestasis was induced by double ligation of the common bile duct and cut between the ligatures. Animals were sacrificed at day 3 and at week 1, 2, 4, 6, and 8 after BDL. The number of TUNEL positive cells was increased significantly after 3 days of BDL, decreased over 2 weeks and remained constant thereafter. Fas expression was not changed and activation of caspase 8 did not occur. Fas immunoreactivity was exclusively observed in the cytoplasm of hepatocytes, indicating that Fas expressed in rat hepatocytes is a soluble form. Hepatocyte apoptosis was associated with Bax expression, which showed a peak at day 3 and decreased over time gradually. Immnunostaining of Bax was observed in hepatocytes and bile duct epithelial cells (BEC) of control and BDL rats. Bcl-2 was increased over time in BDL rats. These results suggest that apoptosis of hepatocytes in BDL rats is independent of Fas and controlled by Bax expression.
Subcutaneous Toxicity Study of Saposhnikovia divaricata (Turcz.) Schischk in Rats
Toxicological Research, volume 19, issue 1, 2003, Pages 73~82
To evaluate influence of Saposhnikovia divaricata (Turcz.) Schischk extract on rat, Saposhnikovia divaricata (Turcz.) Schischk extract was diluted with 0.9% saline (100 mg/ml/kg, 10 mg/ml/kg, and 1 mg/ml/kg, respectively), and each of diluted test material extract was daily treated subcutaneously for 4 weeks and single-treated subcutaneously for 2 weeks. There were no significances in body weight analysis, urinary analysis, and ophthalmological test. However, in serum biochemical analysis and hematological analysis, we found some significances in high and middle dose group compared with control group. These significances in serum biochemical analysis and hematological analysis may be not induced by test material, because it was not found to be significant from control group in histopathological examination. Therefore, it was concluded that NOEL (No Observed Effect Level) of test material extract may be higher than all treatment doses used in this study, and Saposhnikovia divaricata (Turcz.) Schischk extract may be a non-toxic material.