• Toxicological Research
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• v.18 no.2
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• pp.129-138
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• 2002

The mouse lymphoma assay (MLA) has been recently validated as a sensitive and specific test system to determine the genotoxic potential for a chemical. The objective of this study is to evaluate the utility of MLA for detecting mutagens. Especially, to compare MLA with the in vitro chromosomal aberration test (CA), we performed MLA using the microwell method with three chemicals (hydroxyurea, theophylline and amino acid copper complex), which were reportedly positive in the CA. In cell treated with hydroxyurea, anti-neoplastic agent that blocks DNA replication, evidence of a positive response was obtained without S9 mix for 4 h and 24 h. In addition, analysis of colony size distribution at concentration that gave an elevated mutant fraction showed that hydroxyurea induced a high proportion of small type colonies, indicating that hydroxyurea-induced mutation is associated with large chromosomal deletion. Conversely, negative MLA result was obtained for theophylline, which was wed as central nervous system stimulator. Although theophylline increased the mutant frequency at concentration of 1250 $\mu\textrm{g}$/$\textrm{m}{\ell}$ with S9 mix for 4 h, a concentration-related increase in mutant frequency was not observed. The MLA result of amino acid copper complex was considered equivocal because the positive result was obtained at concentration showing 10% or less RS or RTG. Thus, among 3 CA-positive chemicals, positive MLA result was obtained for one. The other two chemicals were negative and equivocal. However MLA, which evaluates mutagenic potential of chemicals through colony formation by cell grouth, may provide a higher predictivity of carcinogenesis than CA.

• The Journal of Korean Medicine
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• v.32 no.1
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• pp.67-83
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• 2011

Objectives: The purpose of this study was to examine the single dose toxicity with oral administration and genotoxicities of Ssanghwa-tang fermented with Lactobacillus acidophyllus. Materials and Methods: Clinical signs, weight changes, lethal doses$(LD_{50})$, and postmortem evaluation were determined by Globally Harmonized Classification System(GHCS) in a single-dose oral toxicity study. In vitro mammalian chromosomal aberration test was conducted with Ames test by cell proliferation suppression assessment using the cultivated CHO-K1(Chinese hamster ovary fibroblast) origins. Bacterial reversion assay was performed using Salmonella typhimurium (TA98, TA100, TA1535, and TA1537) and Escherichia coli (WP2uvrA). In vivo micronucleus test was performed using ICR mouse bone marrow. Results: No clinical sign was observed and none of the groups with doses up to 2000 mg/kg showed significant acute oral toxicity in the single dose oral administration. None of the sample doses taken during the 6 to 18 hour groups showed significant aberrant metaphases comparing to the negative control group in the in vitro mammalian chromosomal aberration test. No evidence of mutagenicity was seen for Escherichia coli (WP2uvrA) or Salmonella typhimurium (TA98, TA100, TA1535, and TA1537). No significant increase in the frequency of micronuclei was seen in the micronucleus test. Conclusion: These results indicate that the $LD_{50}$ value of Ssanghwa-Tang fermented with Lactobacillus acidophyllus may be over 2000 mg/kg and it have no acute oral toxicity and genotoxicity.

• Korean Journal of Animal Reproduction
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• v.26 no.4
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• pp.385-394
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• 2002

This study was constructed the correlations of the embryonic developmental rates and the frequency of chromosome aberration using ear-skin-fibroblast cell in nuclear transfer (NT) derived embryos. Karyoplast-oocyte complexes were fused and activated simultaneously, then cultured for seven days to assess development. The developmental rates of NT and in vitro fertilization (IVF) embryos were 55.4% vs 63.5%, 31.7% vs 33% and 13.4% vs 16.8% in 2 cell, 8 cell and blastocyst, respectively. Firstly, the frequency of chromosome aberrations were evaluated using fluorescent in situ hybridization (FISH) technique with porcine chromosome 1 submetacentric specific probe. Chromosome aberration was detected at day 3 on the embryo culture, the percentages of chromosomal aneuploidy in NT and IVF embryos at 4-cell stage were 40%, 31.3%, respectively. Secondly, embryonic fragmentation was evaluated at 4-cell stage embryo. Frequency of embryonic fragmentations was in 51.3% of NT, 61.3% of IVF, 28.9% of parthenogenetic activation at 4-cell stage. The proportion of fragmentation in NT embryos was higher than activation embryos. This result indicates that chromosomal abnormalities and embryonic fragments are associated with low developmental rate in porcine NT embryo. It is also suggest that abnormal porcine embryos produced by NT related with lower implantation rate, increased abortion rate and production of abnormal fetuses.

• Environmental Analysis Health and Toxicology
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• v.24 no.1
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• pp.43-52
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• 2009

Fullerene의 유전독성을 평가하기 위하여 Chinese hamster유래의 난소유아세포(CHO-K1 cell)를 이용하여 직접법(-S9)과 대사활성화법(+S9 mix)의 염색체이상시험을 실시하였다. 시험물질은 1% CMC 나트륨염의 현탁액(1% CMC 용액)에 희석하여 조제하였다. 대사활성화를 시키지 않은 직접법의 염색체이상시험에서 24시간 투여군은 8단계의 농도(0.078, 0.156, 0.313, 0.625, 1.25, 2.5, 5, 10 mM)로 투여하여 실시하였다. 투여 농도 증가에 따른 염색체이상의 빈도가 증가하는 양상이 나타나지 않았다. 48시간의 투여군에서는 8단계의 농도(0.078, 0.156, 0.313, 0.625, 1.25, 2.5, 5, 10 mM)로 투여하여 실시하였는데 투여 농도 증가에 따른 염색체이상의 빈도가 증가하는 양상이 나타나지 않았다. 배수체의 염색체이상은 직접법에서 관찰되지 않았다. 대사활성화법을 이용하여 6시간 시험물질을 투여한 시험에 있어서는 8단계의 용량단계(0.078, 0.156, 0.313, 0.625, 1.25, 2.5, 5, 10mM)를 설정하였는데 투여 농도가 증가함에 따른 염색체이상빈도의 증가양상이 관찰되지 않았다. 이상의 결과를 종합할 때 본 시험물질은 본 시험 조건하에서 CHO-K1세포에서 대사활성화를 시켰을 때 염색체이상을 유발하지 않는 것으로 판단된다.

• YAKHAK HOEJI
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• v.42 no.5
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• pp.527-533
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• 1998

6-(3,4-Dichlorophenyl)amino-7-chloro-5,8-quinolinedione (RCK50) was tested for antifungal activities in mice systemically infected with Candida albicans. The therapeutic potential of RCK50 was also assessed in comparison with ketoconazole. CK50 had $ED_{50}$ 0.22${\pm}$0.01mg/kg. Ketoconazole as a positive control had $ED_{50}$ 6.00${\pm}$1.70mg/kg. Intraperitoneally administered RCK50 at the $ED_{50}$ for 7 days and 14 days reduced Candida albicans colony count in the kidneys and liver. And administered RCK50 at the $ED_{50}$ for 14 days improved survival rates. The genotoxicities of RCK50 had been evaluated. RCK50 was negative in Ames test with Salmonella typhimurium and chromosomal aberration test in CHL cells. RCK50 did not show any clastogenic effect in mouse peripheral blood and was negative in mouse micronucleus assay. These results indicate that RCK50 has no genotoxic potential under these experimental conditions. Acute oral toxicity studies of RCK50 were carried out in ICR mice of both sexes. RCK50 did not show acute oral toxicities and $LD_{50}$ values were over 2,850mg/kg in ICR mice.

• Food Science and Preservation
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• v.16 no.5
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• pp.782-788
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• 2009

The genotoxicological safety of gamma-irradiated egg white and yolk was examined to ensure that required safety parameters were met, and in an effort to further apply gamma-irradiation for improvement of the hygienic qualities of eggs. Egg white and yolk were irradiated at 20 kGy, much higher than the legally approved dose (less than 5 kGy), and possible genotoxicity was evaluated using in vitro and in vivo tests. The SOS chromotest employing Escherichia coli PQ37, and a chromosomal aberration test in cultured Chinese hamster lung (CHL) cells, were performed in vitro with or without metabolic activation (S9). An in vivo micronucleus development test was conducted using mouse bone marrow cells. Negative results were obtained in the SOS chromotest. The incidence of chromosomal aberration in CHL cells and the frequency of micronuclear developmentin mouse bone marrow cells treated with irradiated samples were not significantly different from those of non-irradiated controls. Thus, it may be concluded that up to 20 kGy of gamma irradiation applied to egg white and yolk did not show any genotoxic effects under our experimental conditions.

• Toxicological Research
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• v.25 no.1
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• pp.51-58
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• 2009

Carrageenan is a naturally-occurring sulfated polygalactan which has been widely used in the dairy industry and a gelling agent in non-dairy products. In this study, four short-term in vitro genotoxicity assays were investigated to evaluate the potential genotoxic effects of carrageenan. The mutagenicity of carrageenan was evaluated up to a maximum dose of 5 mg/plate in Ames test. There was no increase in the number of revertant colonies compared to its negative control at any dose in all of strains tested. To assess clastogenic effect, the in vitro chromosomal aberration assay was performed using Chinese hamster lung cells. Carrageenan was not considered to be clastogenic in this assay at up to the highest feasible concentration which could be evaluated. The in vitro comet assay and micronucleus test results obtained on L5178Y cells also revealed that carrageenan has no genotoxicity potential, although there was a marginal increase in micronuclei frequencies and DNA damage in the respective micronucleus and comet assays. Taken together, our results indicate that carrageenan was not genotoxic based on four in vitro genotoxicity results.

• Journal of Ginseng Research
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• v.43 no.4
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• pp.562-571
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• 2019

Background: Ginsenosides have been widely used clinically for many years and were regarded as very safe. However, a few researches on the toxicities of these kinds of agents showed that some ginsenosides may have side-effect on the rats or dogs. So it is extremely necessary to further clarify the potential toxicity of ginsenosides. This study was carried out to investigate long-term toxicity and genotoxicity of 25-methoxydammarane-3, 12, 20-triol ($25-OCH_3-PPD$), a new derivative of ginsenoside, in beagle dogs. Methods: Twenty-four beagle dogs were divided randomly into four treatment groups and repeatedly orally administered with $25-OCH_3-PPD$ capsule at 60, 120, and 240 mg/kg/day for 91 consecutive days. Ames, micronucleus, and chromosomal aberration tests were established to analyze the possible genotoxicity of $25-OCH_3-PPD$. Results: There was no $25-OCH_3-PPD$einduced systemic toxicity in beagle dogs at any doses. The level of $25-OCH_3-PPD$ at which no adverse effects were observed was found to be 240 mg/kg/day. The result of Ames test showed that there was no significant increase in the number of revertant colonies of $25-OCH_3-PPD$ administrated groups compared to the vehicle control group. There were also no significant differences between $25-OCH_3-PPD$ administrated groups at all dose levels and negative group in the micronucleus test and chromosomal aberration assay. Conclusion: The highest dose level of $25-OCH_3-PPD$ at which no adverse effects were observed was found to be 240 mg/kg per day, and it is not a genotoxic agent either in somatic cells or germs cells. $25-OCH_3-PPD$ is an extremely safe candidate compound for antitumor treatment.

• Journal of Physiology & Pathology in Korean Medicine
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• v.34 no.6
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• pp.355-361
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• 2020

This study was designed to assess the toxicity of capsaicin-containing (CP) pharmacopunture using an in vitro chromosomal aberrations in Chinese hamster lung (CHL/IU) cells. In order to determine the high dose level in the main study of this study, a dose range finding study was conducted first. The high dose was selected at 10.0% of CP pharmacopuncture extract, and then diluted sequentially to produce lower dose levels of 5.00, 2.50, 1.25, 0.625 and 0.313% by applying a geometric ratio of 2. As a result, the cytotoxicity and precipitation of the CP pharmacopuncture as a test substance were not evident at any dose level during short-time treatment with and without metabolic activation and continuous treatment without metabolic activation. Therefore, the dose levels for this study were chosen as 10.0, 5.0, and 2.5%., and the treatment volume was 1.3 mL. In addition, negative and positive controls were set. In main study, the frequency of cells with chromosome aberrations in CP treated groups was less than 5% in short-time treatment with and without metabolic activation and continuous treatment without metabolic activation. In addition, there was no statistically significant difference when compared to the negative control group. The frequency of cells with structural chromosomal aberrations in the positive control group was more than 10% compared to the negative control group, and it increased statistically significantly. In conclusion, under the conditions of this study, CP pharmacopuncture did not show the possibility of causing chromosome aberrations.

• Clinical and Experimental Pediatrics
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• v.59 no.sup1
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• pp.19-24
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• 2016

Constitutional interstitial deletions of the long arm of chromosome 5 (5q) are quite rare, and the corresponding phenotype is not yet clearly delineated. Severe mental retardation has been described in most patients who present 5q deletions. Specifically, the interstitial deletion of chromosome 5q33.3q35.1, an extremely rare chromosomal aberration, is characterized by mental retardation, developmental delay, and facial dysmorphism. Although the severity of mental retardation varies across cases, it is the most common feature described in patients who present the 5q33.3q35.1 deletion. Here, we report a case of a de novo deletion of 5q33.3q35.1, 46,XY,del(5)(q33.3q35.1) in an 11-year-old boy with mental retardation; to the best of our knowledge this is the first case in Korea to be reported. He was diagnosed with severe mental retardation, developmental delay, facial dysmorphisms, dental anomalies, and epilepsy. Chromosomal microarray analysis using the comparative genomic hybridization array method revealed a 16-Mb-long deletion of 5q33. 3q35.1(156,409,412-172,584,708)x1. Understanding this deletion may help draw a rough phenotypic map of 5q and correlate the phenotypes with specific chromosomal regions. The 5q33.3q35.1 deletion is a rare condition; however, accurate diagnosis of the associated mental retardation is important to ensure proper genetic counseling and to guide patients as part of long-term management.