• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.5
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• pp.1145-1153
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• 2009

The object of this study was to obtain acute information single oral dose toxicity of Mahwangbujaseshin-tang extracts, with mouse bone marrow cell micronucleus test for detecting possible genotoxicity. In order to observe the 50% lethal dose, approximate lethal dosage, maximum tolerance dosage and target organs, test articles were once orally administered to ICR mice at dose levels of 2000, 1000, 50 mg/kg according to the recommendation of KFDA Guidelines. The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after dosing according to KFDA Guidelines with organ weights of 12 types of principle organs. In addition, after twice oral treatment of Mahwangbujaseshin-tang extracts 2000, 1000 and 500 mg/kg, we checked the changes on the number of MNPCE. We could not find any mortality, clinical signs, changes in the body weight and gross findings upto 2000 mg/kg treated group. The limited dosages in rodents except for increases of lymphoid organ weights and hypertrophy encounted as results from pharmacological effects of Mahwangbujaseshin-tang extracts, immune modulator effects with some sporadic accidental findings not toxicological signs. No evidence of increases of MNPCE numbers were also detected in all three different dosages of Mahwangbujaseshin-tang extracts treated mice. The results obtained in this study suggest that the LD50 and ALD of Mahwangbujaseshin-tang extracts in mice were considered as over 2000 mg/kg because no mortalities were detected upto 2000 mg/kg that was the highest dose recommended by KFDA and OECD. And the results of mouse bone marrow micronucleus test of Mahwangbujaseshin-tang extracts is negative results.

• Toxicological Research
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• v.24 no.2
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• pp.151-159
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• 2008

Rhus verniciflua Stokes(RVS), one of traditional medicinal plants in Asia, was found to have pharmacological activities such as antioxidative and antiapoptotic effects, raising the possibility for the development of a novel class of anti-cancer drugs. Thus, potential genotoxic effects of RVS in three short-term mutagenicity assays were investigated, which included the Ames assay, in vitro Chromosomal aberration test, and the in vivo Micronucleus assay. In Ames test, the addition of RVS water extracts at doses from 313 up to 5000 mg/plate induced an increase more than 2-fold over vehicle control in the number of revertant colonies in TA98 and TA1537 strains for detecting the frame-shift mutagens. The similar increase in reversion frequency was observed after the addition of RVS ethanol extracts. To assess clastogenic effect, in vitro chromosomal aberration test and in vivo micronucleus assay were performed using Chinese hamster lung cells and male ICR mice, respectively. Both water and ethanol extracts from RVS induced significant increases in the number of metaphases with structural aberrations mostly at concentrations showing the cell survival less than 60% as assessed by in vitro CA test. Also, there was a weak but statistically significant increase in number of micronucleated polychromatic erythrocytes(MNPCEs) in mice treated with water extract at 2000 mg/kg while ethanol extracts of RVS at doses of up to 2000 mg/kg did not induce any statistically significant changes in the incidence of MNPCEs. Therefore, our results lead to conclusion that RVS acts as a genotoxic material based on the available in vitro and in vivo results.

• Molecular & Cellular Toxicology
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• v.5 no.3
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• pp.257-264
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• 2009

Gardenia yellow, extracted from gardenia fruit, has been widely used as a coloring agent for foods, and thus, safety of its usage is of prime importance. In the current study, short-term genotoxicity assays were conducted to evaluate the potential genotoxic effects of gardenia yellow. The gardenia yellow used was found to contain 0.057 mg/g of genipin, a known biologically active compound of the gardenia fruit extract. Ames test did not reveal any positive results. No clastogenicity was detected by a chromosomal aberration test, even on evaluation at the highest feasible concentration of gardenia yellow. Gardenia yellow was also shown to be non-genotoxic using an in vitro comet assay and a micronucleus test with L5178Y cells, although a marginal increase in DNA damage and micronuclei frequency was reported in the respective assays. Additionally, in vivo micronucleus test results clearly demonstrated that oral administration of gardenia yellow did not induce micronuclei formation in the bone marrow cells of male ICR mice. Taken together, our results indicate that gardenia yellow is not mutagenic to bacterial cells, and that it does not cause chromosomal damage in mammalian cells, either in vitro or in vivo.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.1
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• pp.124-133
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• 2010

The object of this study was to obtain acute information single oral dose toxicity of Mahwangbujaseshin-tang extracts, with mouse bone marrow cell micronucleus test for detecting possible genotoxicity. In order to observe the 50% lethal dose, approximate lethal dosage, maximum tolerance dosage and target organs, test articles were once orally administered to ICR mice at dose levels of 2000, 1000, 50 mg/kg according to the recommendation of KFDA Guidelines. The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after dosing according to KFDA Guidelines with organ weights of 12 types of principle organs. In addition, after twice oral treatment of Mahwangbujaseshin-tang extracts 2000, 1000 and 500 mg/kg, we checked the changes on the number of MNPCE. We could not find any mortality, clinical signs, changes in the body weight and gross findings upto 2000 mg/kg treated group. The limited dosages in rodents except for increases of lymphoid organ weights and hypertrophy encounted as results from pharmacological effects of Mahwangbujaseshin-tang extracts, immune modulator effects with some sporadic accidental findings not toxicological signs. No evidence of increases of MNPCE numbers were also detected in all three different dosages of Mahwangbujaseshin-tang extracts treated mice. The results obtained in this study suggest that the LD50 and ALD of Mahwangbujaseshin-tang extracts in mice were considered as over 2000 mg/kg because no mortalities were detected upto 2000 mg/kg that was the highest dose recommended by KFDA and OECD. And the results of mouse bone marrow micronucleus test of Mahwangbujaseshin-tang extracts is negative results.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.1
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• pp.182-192
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• 2004

Gamma irradiation at 5 and 10 kGy was applied to Kwamegi (semi-dried Colobabis seira) for their possible hygiene quality and carried out genotoxicological safety. In vitro genotoxicological safety of each 5 and 10 kGy-irradiated Kwamegi was evaluated by Salmonella typhimurium (TA98, TA100, TA1535 and TA1537) and E. coli WP2 uvrA reversion assay, SOS chromotest (Escherichia coli PQ37) and chromosome aberration test (Chinese hamster lung fibroblast cells) in the absence and presence of an exogenous metabolizing system (S9 mix). Gamma-irradiated samples were not different from nonirradiated-control to respective in vitro tests. And in vivo micronucleus test using ICR mice (male) micronucleus was not observed. Kwamegi exposed to 10 kGy-gamma ray revealed negative results in these three in vitro mutagenetic tests and in vivo micronucleus test up to 10,000 $\mu\textrm{g}$/plate, respectively. The results indicated that 5 and 10 kGy gamma-irradiated Kwamegi (semi-dried Colobabis seira) did not have mutagenicity.

• Biomolecules & Therapeutics
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• v.6 no.1
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• pp.56-62
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• 1998

Mutagenicity of recombinant human erythropoietin (rhEPO) was examined in the reverse mutation test on bacteria, in the chromosomal aberration test on cultured mammalian cells and in the micronucleus test on mice. The reverse mutation test was performed by a plate incorporation method with or wothout a metabolic activation system (59 Mix) using Salmonella typhimurium strain TA100, TA1535, TA98 and TA 1537. The rhEPO did not significantly increase revertant colonies in any of the test strains under any conditions at dose levels ranging from 1000 H/ml to 62.5 lu/plate, compared with the vehicle control. In the chromosomal aberration test using cultured Chinese Hamster Lung (CHL) cells, the number of aberrant cells was not increased in the presence or absence of 59 Mix at concentrations of 1000 lU/ml to 250 lU/ml, compared with the vehicle control. In the micronucleus test, male ICR mice were given rhEPO intraperitoneally at a dose level of 25000, 12500 and 6250 lU/kg. The incidence of bone marrow micronucleated polychromatic erythrocytes was not different from that of the vehicle control. From these results, rhEPO is considered to be non-mutagenic under the present test conditions.

• Biomolecules & Therapeutics
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• v.4 no.3
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• pp.224-231
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• 1996

DA-5018, a non-narcotic analgesic agent, was examined for mutagenicity in the reverse mutation test on bacteria, chromosomal aberration test on cultured mammalian cells and micronucleus test on mice. The reverse mutation test was performed by a plate incorporation method with or without a metabolic activation system(S9 mix) using Salmonella typhimurium strain TA100, TA1535, TA98 and TA1537. DA-5018 did not significantly increase revertant colonies in any of the test strains under any conditions at concentrations ranging from 0.0049 to 1.25 mg/plate, compared with the vehicle control. In the chromosomal aberration test using cultured Chinese Hamster Lung(CHL) cells, DA-5018 did not increase the number of aberrant cells in the presence or absence of S9 mix at concentrations of 0.016 mM/plate to 0.25 mM/plate, compared with the vehicle control. In the micronucleus test, male ICR mice were given DA-5018 intraperitoneally at a dose level of 0.55, 1.10 and 2.20 mg/kg. The incidence of bone marrow micronucleated polychromatic erythrocytes in the DA-5018 treated mice was not significantly different from that of the vehicle control. These results indicate that DA-5018 does not have mutagenic potential under the present test conditions.

• Journal of Radiation Protection and Research
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• v.24 no.4
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• pp.225-230
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• 1999

This study was carried out to investigate the radiation dose-response of micronucleus frequencies in Tradescantia pollen mother cells. The number of micronuclei increased in the tetrads as a result of chromosome deletion after irradiation. The maximal frequency of micronuclei showed a good dose-response relationship in the range of dose $0{\sim}50$ cGy. On the basis of the relationship, a dose of 1 cGy results maximally in two additional micronuclei in 100 tetrads. The radiation dose-response relationship of micronucleus occurrence is prerequisite to biological monitoring of radiations. The micronucleus assay can be applied to biological risk assessment of environmental toxicants, and to integrity test of water or soils of interest.

• Biomolecules & Therapeutics
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• v.4 no.3
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• pp.239-243
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• 1996

DW-116 {(1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-1-piperazinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid hydrochloride) is a new quinolone antibiotic with a broad antibacterial spectrum against G(+) and G(-) bacteria. DW-116 was evaluated for the appearance of micronucleus in polychromatic erythrocytes (PCEs) of mouse bone marrow cells after intraperitoneal and oral single administration. We prepared the bone marrow cells at 30hr after drug administration and they were used for measuring PCE with micronucleus. The results showed there was no statistically significant increase in the numbers of PCEs with micronucleus in all DW-116 administered groups compared with a negative control group. The results also showed that the ratio of normochromatic erythrocytes(NCEs) to PCEs of all DW-116 administered groups was not significantly different from that of a negative control group. These results suggested that DW-116 may not cause any chromosomal damage and it has no in vivo mutagenic potential under these experimental conditions.

• Safety and Health at Work
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• v.1 no.1
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• pp.80-86
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• 2010

Objectives: We investigated the genotoxicity of two chemicals, methyl formate and 2-methylbutane, using male ICR mice bone marrow cells for the screening of micronucleus induction. Although these two chemicals have already been tested numerous times, a micronucleus test has not been conducted and the amounts used have recently been increased. Methods: 7 week male ICR mice were tested at dosages of 250, 500, and 1,000 mg/kg for methyl formate and 500, 1,000, and 2,000 mg/kg for 2-methlybutane, respectively. After 24 hours of oral administration with the two chemicals, the mice were sacrificed and their bone marrow cells were prepared for smearing slides. Results: As a result of counting the micronucleated polychromatic erythrocyte (MNPCE) of 2,000 polychromatic erythrocytes, all treated groups expressed no statistically significant increase of MNPCE compared to the negative control group. There were no clinical signs related with the oral exposure of these two chemicals. Conclusion: It was concluded that the two chemicals did not induce micronucleus in the bone marrow cells of ICR mice, and there was no direct proportion with dosage. These results indicate that the two chemicals have no mutagenic potential under each study condition.