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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Journal DOI :
The Korean Society of Toxicology
Editor in Chief :
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
The Recommended Approaches for the Evaluation of Testicular Toxicity with Awareness of the Spermatogenic Cycle and Quantitative Testicular Toxicity Evaluation Methods
Toxicological Research, volume 19, issue 2, 2003, Pages 83~90
Since histopathological examination was known to be the most sensitive evaluation for testicular toxicity, regulatory authorities have been published the guidelines on practical testicular assay approach. Those guidelines specified details of evaluation including fixation, embedding, stain-ing, histological examination and also seminiferous tubular staging methods. However, there have been confusing understanding among toxicologists and even pathologists on staging theory and its application on industrial testicular toxicity. Guidelines did not intend to conduct quantitative assay with staging but recommended the use of knowledge of staging. To count each tubular stage with statistical analysis is known to be time consuming and labor burdening work but the significance of toxicity has little value. It also has been pointed out that the application of staging theory for longer-term toxicity considered to be lacking of rationale. It could be recommended that qualitative assay with aware-ness of germ cell loss is more efficient method rather than quantitative counting of each tubular stage. Therefore it would be required that comprehensive understanding of testicular toxicity evaluation and the use of testicular staging method.
Induction of Apoptosis by N-methyl-N'-nitro-N-nitrosoguanidine, an Alkylating Agent, in Human Prostate Carcinoma Cells
Toxicological Research, volume 19, issue 2, 2003, Pages 91~98
Alkylating agents form alkylated base adducts in the DNA and cause DNA lesions leading to cell killing. In this study, we investigated the mechanism of apoptosis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in PC-3 and DU145 human prostate carcinoma cell lines. MNNG treatment resulted in the inhibition of cell proliferation in a concentration-dependent manner to a similar extent in both cell lines. This anti-proliferative effect of PC-3 and DU145 cells by MNNG was associated with morphological changed such as membrane shrinking, cell rounding up and formation of apoptotic bodies. MNNG treatment also induced a proteolytic cleavage of specific target proteins such as poly(ADP-ribose) polymerase (PARP) and
-catenin proteins in DU145 cells but in PC-3 cells. Furthermore, we observed an increase of proapoptotic protein Bax family expression and a decrease of antiapoptotic protein Bcl-2 family by MNNG treatment in a concentration-dependent manner MNNG also induced a proteolytic activation of caspase-3 and -9, which is believed to play a central role in the apoptotic signaling pathway.
Oxygen Toxicity: Behavioral Assessment by Swim Test in Mouse Exposed to Hypoxia and Hyperoxia
Toxicological Research, volume 19, issue 2, 2003, Pages 99~104
This study was aimed to evaluate the effect of oxygen on motor activity and toxicity in male mice. The modified Porsolt forced swim test (FST) was used and the distance and time of movement by mice were analyzed in 15。C water bath for 20 minutes using the automatic Ethovision videotracking system. Analyses were carried out before and after 20 minutes of exposure to 10％-70％ concentration of normobaric oxygen. The effects of inspired oxygen tension on the distance and time of movement showed the similar trends, but changes in distance were more prominent. Both the distance and time of movement increased after exposure to 30％ and 40％ oxygen concentration. The distance and time of movement also increased upon exposure to 50％ and 60％ oxygen. In contrast, increases En movement and time under exposure to 21％ oxygen concentration were suppressed when exposed to over 50％ oxygen concentration. With exposure to 10％ oxygen, there was a significant decrease in the distance of movement and a slight suppression of movement time. During the swim test, 12.5％, 37.5％, and 87.5％ of the mice drowned after exposure to 10％, 60％, and 70％ oxygen concentration, respectively. These results suggest that motor activity can be enhanced by inspired oxygen up to 40％ concentration. When hypoxic and hyperoxic oxygen exposure over 50％, motor activity is reduced and toxicity may be induced.
Effect of Cyclohexane Treatment on the Liver Damage in CCl
Toxicological Research, volume 19, issue 2, 2003, Pages 105~114
TO evaluate an effect of cyclohexane treatment on the degree of liver damage, rats were induced liver damage with 10 or 17 times
injection (0.1 m1/100 g body wt., 50%
dis-solved in olive oil) at intervals of every other day. Cyclohexane (1.56 g/kg body wt., i.p.) was administrated to the animals at 48 hours after the last pretreatment of
. Rats were sacrificed at 4 hours after injection of cyclohexane. On the basis of histopathological findings, liver weight/body weight (LW/ BW, %), activities of serum alanine aminotransferase (ALT), xanthine oxidase (XO) and akaline phosphatase (ALP), and contents of liver protein and manlondialdehyde (MDA),
-pretreatment induced liver damage. And
17 times treated group showed more severe liver damage than
10 times treated group. Administration of one dose of cyclohexane to
10 times treated animals resulted in the enhanced liver damage; liver necrosis with proliferation of fibroblast and bile duct abnormality, and increase in hepatic MDA content and the activities of serum ALP and ALT, But the enhanced liver damage was not found in
17 times treated animals. Serum cyclohexanone concentrations at 4 or 8 hours after injection of cyclohexane were higher in all liver damaged groups than normal group and were somewhat higher In
17 times treated animals than
10 times treated ones. Among the oxygen free radical metabolizing enzymes, hepatic cytochrome P45O dependent aniline hydroxylase (CYPdAH) activity in cyclohexane metabolizing enzyme system was meaningfully increased by the injection of cyclohexane to the liver damaged rats, with increased Vmax and high affinity to aniline. LW/BW (%) and activities of serum XO and ALT were more significantly increased in liver damaged groups than normal group by administration of cyclohexanone. In conclusion, it is assumed that an enhancement of liver damage by injection of one dose of cyclohexane to liver damaged animals might be caused by oxygen free radicals and cyclohexanone.
Muscle-Specific Creatine Kinase Gene Polymorphisms in Korean Elite Athletes
Kang, Byung-Yong ; Kang, Chin-Yang ; Lee, Kang-Oh ;
Toxicological Research, volume 19, issue 2, 2003, Pages 115~121
In view of the importance of muscle-specific creatine kinase (CKMM) gene as a genetic factor for athletic performance, we investigate the relationship between elite athletic performance and two restriction fragment length polymorphisms (Ncol and Taql RFLPs) in the CKMM gene. Genomic DNA was extracted from white blood cells of 98 unrelated male Korean elite athletes and 04 sedentary controls, respectively. Two genetic polymorphisms in the CKMM gene were detected by the polymerase chain reaction and the digestion with restriction endonucleases, Ncol and Taql, respectively. There were no significant associations between two genetic polymorphisms in the CKMM gene and elite athletic performance or clinical parameters in our subjects. Therefore, these findings suggest that two genetic polymorphisms in the CKMM gene may not be useful as genetic markers to predict the athletic performance in male Koreans.
Combined Repeated Dose and Reproductive/Developmental Toxicities of Benzoyl Peroxide
Toxicological Research, volume 19, issue 2, 2003, Pages 123~131
This study was carried out to assess the combined repeated dose, reproduction and developmental toxicities of benzoyl peroxide for OECD SIDS (Screening Information Data Set) program. Male and female Sprague-Dawley rats were exposed to benzoyl peroxide at dose levels of 0, 250, 500 and 1,000 mg/kg/day for 29 days for males and for 41-51 days for females. No deaths were found in all animals including control group during exposure period. No hematological effects attributable to benzoyl peroxide were observed in all treated groups. Significant decrease in the weight of testes and epididymis were observed in males at 1,000 mg/kg/day. In females at 1,000 mg/kg/day, slight histopathological effects in uterus such as epithelial vacuolation or hyperplasia were observed. No treatment-related changes in precoital time and rate of copulation, fertility and gestation period were noted in all treated groups. There was no evidence of teratogenic effect of benzoyl peroxide, but body weight of pups at 1,000 mg/kg/day was significantly decreased. NOAEL for combined repeated dose and reproduction/developmental toxicity was 500 mg/kg/day.
A Non-radioisotopic Endpoint Using Bromodeoxyuridine ELISA Method for Murine Local Lymph Node Assay
Toxicological Research, volume 19, issue 2, 2003, Pages 133~139
Allergic contact dermatitis may be caused by a wide variety of chemicals. A murine local lymph node assay (LLNA) has been developed as an alternative to guinea pig models for assessing the contact sensitization potential of chemical. However, there is a need to develop a nonradioisotopic endpoint for the LLNA, because of the radioisotopic method's requiring the use of special facilities. In this study, we investigated the development of a nonradioisotopic endpoint for LLNA using ELISA (enzyme-linked immunosorbent assay). Female Balb/c mice were treated by the topical application on the dorsum of both ears with four different strong sensitizers, 2,4-dinitrochlorobenzene (DNCB), oxazolone (OXZ), toluene diisocyanate (TDI), and trimellitic anhydride (TMA), and a strong irritant, sodium lauryl sulfate (SLS), once daily for three consecutive days. The proliferation of cells in the auricular Iymph node was analyzed by means of the labelling index (Ll) of bromodeoxyuridine (BrdU) incorporation into cells. The weights of the Iymph nodes in the mice treated with allergens, DNCB, OXZ, TDl and TMA were increased compared to the vehicle control. The stimulation index (Sl) of mice treated with DNCB, OXZ, TDl, and TMA was over three-fold increase compared to the vehicle control. However, the S1 of mice exposed to SLS was not significantly increased compared to the vehicle control, while the lymph node weight of SLS was significantly increased. These results suggest that the LLNA modified endpoint using ELISA based on BrdU incorporation could provide a useful method of screening for irritants and allergens.
Mutagenicity Studies on Nonspecific Immunostimulator BARODON
Toxicological Research, volume 19, issue 2, 2003, Pages 141~146
A nonspecific immunostimulator
was tested for mutagenicity using Ames Salmonella tester strains TA98, TA1 00, TA 102, TA 1535 and TA 1537 with or without metabolic activation (59 mix). None of the fresh species showed mutagenicity. In the reverse mutation test using Salmonella phimurium TA98, TA100, TA102, TA1535 and TA1537 did not increase the number of revertants at all doses tested (5, 2.5 or 1.25 mg/ml). Chromosome aberration test was carried out in Chinese hamster lung (CHL) cell line. The cells were treated with
(1, 0.5 or 0.25 mg/ml), while positive control group was treated with Mitomycin C (0.1 mg/ml). The results show that there is no statistically significant difference between positive control and treatment groups. In mouse micronucleus test, there was significant increase in the ratio of micronucleated polychromatic erythrocyte (MNPCE) in the high dose group (10%
), while there is no significance between control and low (2.5%
) or middle (5%
dose groups. Taken together, this results suggest that below 5%
might not have mutagenic potential in vitro and vivo systems.
Antitumor Activities to Cytotoxicity of Phellinus linteus Ethanol Extract
Toxicological Research, volume 19, issue 2, 2003, Pages 147~152
We investigated antitumor activities of the ethanol extract from mushroom Phellinus linteus and Phellinus baumii on mulberry, oak and elm. in vitro test, the ethanol extract of mushroom cultivated on oak of Phellinus linteus showed highest activities about SK-OV-3, HCT15, XF498, SK-MEL-2 and A549. SK-OV-3 cell line showed 100% cytotoxicity in 100
/ml and HCT15 (98.39%), XF498 (89.62%), SK-MEL-2 (84.07%) and A549 (79.92%) cytotoxicity respectively. Also
/ml to SK-OV-3 cell line and HCT15 (4.37
/ml), A549 (5.48
/ml), SK-MEL-2 (6.72
/ml), XF 498 (6.88
/ml). As those results, cultivated oak of Phellinus linteus showed a very low
value against SK-OV-3, HCT15, XF498, SK-MEL-2 and A549 cancer cell lines.
Localization of Methyl Mercuric Chloride in the Reproductive Tract of Male Mice
Choe, Eun-Sang ; Kim, Kuk-Ryul ; Yee, Sung-Tae ; Kim, Myung-Hoon ; Min, Byung-Woon ; Cho, Hyun-Wook ;
Toxicological Research, volume 19, issue 2, 2003, Pages 153~159
Localization of mercury compounds was investigated in selective regions of the male reproductive tract using autometallography. The results demonstrated that mercury was observed in Sertoli and Leydig cells in testis, but not in the epithelial cells of rete testis and germ cells. In the efferent ductule, mercury compounds were observed in the cytoplasmic compartments of epithelial cells in the proximal and common regions, while they were observed in the supranuclear cytoplasmic compartments in the conus region. In the epididymis, the compounds were observed in the cytoplasmic compariments of narrow and basal cells, but not in the principal cells of the initial segment. In contrast, the compounds were evenly detected in the cytoplasmic compartments of principal cells in the caput. In the corpus and caudal epididymis, the compounds were observed in the basal region of principal cells. The data shows that mercury is differentially accumulated in the male reproductive tract in a region-specific manner.