• Korean Journal of Oriental Medicine
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• v.18 no.2
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• pp.151-157
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• 2012

In this research, the genotoxic effect of Bupleuri Radix (BR), the dried roots of Bupleurum falcatum Linne has been traditionally used as anti-inflammatory agent, was evaluated using the mouse micronucleus test. BR aqueous extract (yield = 16.52%) was administered once a day for 2 continuous days by oral gavage to male ICR mice at doses of 2,000, 1,000 and 500 mg/kg. Cyclophosphamide (CPA) 70 mg/kg was used as a known genotoxic agent in a positive control. The appearance of a micronucleus (MN) in polychromatic erythrocyte (PCE) is used as an index for genotoxic potential, and PCE ratio is used as an index of cytotoxicity. Although significant (p<0.01) increase of the number of PCE with one or more nuclei (MNPCE) was detected in CPA treated groups, no significant increases of MNPCE numbers were observed in all three different dosages of BR extracts treated mice with over 0.30 of the individual polychromatic erythrocyte ratio in all mice used in this study. The results obtained indicated that BR extract shows no genotoxicity effects up to 2,000 mg/kg dosing levels the limit dosage in rodents.

• Journal of Society of Preventive Korean Medicine
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• v.16 no.1
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• pp.81-89
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• 2012

Objectives : In this research, the genotoxic effect of $Scutellariae$ $Radix$(SR), the dried roots of $Scutellaria$ $baicalensis$ Georgi has been traditionally used as antipyretic agent, was evaluated using the mouse micronucleus test. Methods : SR aqueous extract(yield = 27.2%) was administered once a day for 2 continuous days by oral gavage to male ICR mice at doses of 2,000, 1,000 and 500 mg/kg. Cyclophosphamide(CPA) 70 mg/kg was used as a known genotoxic agent in a positive control. The appearance of a micronucleus(MN) in polychromatic erythrocyte(PCE) is used as an index for genotoxic potential, and PCE ratio is used as an index of cytotoxicity. Results and Conclusions : Although significant(p<0.01) increase of the number of PCE with one or more nuclei(MNPCE) was detected in CPA treated groups, no significant increases of MNPCE numbers were observed in all three different dosages of SR extracts treated mice with over 0.33 of the individual polychromatic erythrocyte ratio in all mice used in this study. The results obtained indicated that SR extract shows no genotoxicity effects up to 2,000 mg/kg dosing levels - the limit dosage in rodents.

• Biomolecules & Therapeutics
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• v.2 no.3
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• pp.286-291
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• 1994

The mutagenicity of DA-3030(rhG-CSF)was studied by reverse mutation test, chromosome aberration test and micronucleus test. The reverse mutatuon test in bacteria was performed using salmonella typhimurium strain TA100, TA98, TA1535 and TA1537 with rhG-CSF in any of the concentrations(150, 75, 37.5, 18.75, 9.375 and 4,6875 $\mu\textrm{g}$/plate), no increase in the number of revertant colonies in each strain was observed, irrespective of treatment with the metabolic activation system(S-9 mix) The chromosome aberration test was carried out using CHL cells, cell line from chinese hamster lung. With 4 doses(75, 37.5, 18.75 and 9.375 $\mu\textrm{g}$/ml) of rhG-/CSF the cells were treated for 24 or 48 hours in the direct method or for 6 hours followed by 18 hour-expression time in the metabolic activation method. Results of the study showed, by the direct method or metabolic activation method, no trend toward increase in the number of aberrant metaphase. The micronucleus test was carried out using ICR mice at the age of 8 weeks. Three doses(862.5, 1725 and 3450 $\mu\textrm{g}$/kg) of DA-3030 were admintstered intraperitoneally with single shot and bone marrow cells were sampled at 24 hours after administration. Neither the number of polychromatic erythrocytes with micronuclei nor the ratio of normochromatic erythrocytes to polychromatic erythrocytes increased singinficantly in each dose, compared with a vehicle control. These results indicate that rhG-CSF has not mutagenic potential under the condiions.

• Toxicological Research
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• v.3 no.1
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• pp.15-26
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• 1987

The mutagenicity of pranoprofen, a new antiinflammatory agent primarily used in Japan, was evaluated by employing several different methods such as the Ames test, micronucleus test, and the sister chromatid exchange test. For the Ames test, various doses of pranoprofen (5 and 1 mg, 100, 10, and 1 ${\mu}$g per plate) were applied, with or without the mammalian liver S-9 fraction, to the S. typhimurium LT2. For the micronucleus test, 24 hours after administering the various doses of pranoprofen (200, 100, and 50 mg/kg) to male mice by aral intubation, the femura of each group were isolated and the bone marrow samples were prepared. The micronucleated red cells and the ratio of the polychromatic versus the normochroomatic cells were counted. For the sister chromatid exchange test, the maximal non-cytotoxic concentrations (10 to 0.1 mM pranoprofen) were applied to the culture media of the Chinese Hamster Ovary (CHO) cells for 24 hrs. The numbers of revertant colonies did not increase with the increasing doses of pranoprofen when teseted with various strains of S. typhimurium. In the micronucleus test employing mice, the pranoprofen was identkfied to be a non-clastogen and a non-spindle poison. In the sister chromatid exchange test employing the cultured CHO cells, the pranoprofen did not increase the incidences of chromosomal abnormality. Based on these results, pranoprofen was found to have no mutagenic activity.

• Biomolecules & Therapeutics
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• v.1 no.2
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• pp.183-187
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• 1993

The anticlastogenic effect of galangin, flavonoid derivative, was studied in vivo micronucleus test using C57BL/6 mice. The frequencies of micronuclei induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in bone-marrow cells of C57BL/6 mice were significantly decreased by the simultaneous treatment or multiple pre-treatment of galangin. When galangin was orally administered at 0, 0.1, 1.0, or 10.0 mg/kg twice with 24 hr interval, together with intraperitoneally administered MNNG, there were suppressive effects in the tested doses. The most marked suppressive effect was observed in the treatment group of 1.0 mg/kg (64.5%), not in the treatment group of 10.0 mg/kg (36.3%). When galangin was multiply administered at 1/7 or 1 mg/kg for 7 days respectively, galangin showed higher suppressive effect in the treatment group of 1/7 mg/kg (23.5%) rather than in the treatment group of 1 mg/kg (13.5%). In another experiment, galangin was administered at 0.001, 0.01 or 0.1 mg/kg for 1 month respectively. The suppressive effects in one month treatment gradually increased with dose-dependent manner, although suppressive effects were not high. The results showed that galangin was effective in suppressing the frequencies of micronuclei induced by MNNG. Our study indicates that galangin is a potent anticlastogenic agent against MNNG.

• Toxicological Research
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• v.14 no.3
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• pp.453-457
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• 1998

In order to evaluate the mutagenic potential of Intralipidos produced by Greenmate cooperation. We performed Salmonella typhimurium reversion assay, chromosomal aberration test on chinese hamster ovarian cells and in vivo micronucleus assay using mouse bone marrow cells. In the reverse mutation test using Salmonella typhimurium TA98 and TA100, Intralipidos did not increase the number of revertant at any of the concentration tested in this study. Intralipidos did not increase the number of cells having structural or numberical chromosome aberration in cytogenetic test. In mouse micronucleus test, no significant increase were observed in the occurrence of micornucleated polychromatic erythrocytes in ICR male mice intraperitoneally administered with Intralipidos. These results indicate that Intralipidos has no genetic toxicity under these experimental conditions.

• Environmental Mutagens and Carcinogens
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• v.16 no.2
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• pp.103-108
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• 1996

The mutagenic potential of rHu-EPO was evaluated using the short-term genotoxicity tests including Ames, chromosome aberration and micronuclei tests. In Salmonella typhimurium assay, rHu-EPO did not show any mutagenic response in the absence or presence of S9 mix with TA98, TA100, TA1535, and TA1537. In chromosome aberration test, rHu-EPO did not show any significant effect on Chinese Hamster Ovary(CHO) cells compared with control. In micronucleus test using male ICR mice, a dose-dependence increase in the frequency of micronucleuted polychromatic erythrocytes(MNPCEs) was observed in bone marrow cells treated with rHu-EPO. However, it was related to the secondary effect of rHu-EPO and the number of MNPCEs was equal to spontaneous frequency. These results indicate that rHu-EPO does not show any positive response in short-term genotoxicity assays.

• 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.

• YAKHAK HOEJI
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• v.35 no.6
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• pp.466-472
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• 1991

Petroleum ether extracts of panax ginseng C.A. Meyer (GPEE) were tested for the evaluation of anticlastogenic effects against benzo(a)pyrene-induced micronucleated polychromatic erythrocytes using mouse bone marrow micronucleus test. When the GPEE was singly administered before benzo(a)pyrene injection, GPEE showed significant anticlastogenic effect at $50{\sim}200\;mg/kg$. When the GPEE was multiply administered for 5 consecutive days before benzo(a)pyrene injection, GPEE showed potent anticlastogenic effect, even at the low doses, $5{\sim}50\;mg/kg/day$. As a control experiment, GPEE was administered without benzo(a)pyrene injection to demonstrate a clastogenic effect of this extract. When the range of $1{\sim}200\;mg/kg/day$ for 5 consecutive days was administered to mice, it was found that there was no increase of MNPCEs frequency.

• Biomolecules & Therapeutics
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• v.5 no.3
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• pp.278-283
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• 1997

DW-166HC ($^{166}$ Holmium ($^{166}$ Ho)-Chitosan complex) is a new radiopharmaceutic anticancer agent with a broad anti-tumoriginec spectrum, especially against human fepatic cancer. DW-166HC was evaluated for the appearance of micronucleus in polychromatic erythrocytes (PCEs) of mouse bone marrow cells after subcutaneous and intravenous single administration. Bone marrow cells were prepared at 24 hr and 48 hr after DW-166HC-I ($^{165}$ Ho-Chitosan complex cold compound) administration and at 24 hr, 72 hr and 2 weeks after DW-166HC ($^{166}$ Ho-Chitosan complex : hot compound) administration. The results showed there was no statistically significant increase of the numbers of PCEs with micronucleus in all DW-166HC-I administered groups compared with a negative control group but there was statistically significant increase of the numbers of PCEs with micronucleus at 24 hr and 72 hr in all DW-166HC administered groups, which was recovered after 2 weeks from the drug administration. The results also showed the ratio of normochromatic erythrocytes (NCEs) to PCEs of all DW-166HC-I administered groups was not significantly different from that of a negative control group but there was significant difference this ratio at 24hr and 72 hr in all DW-166HC administered groups compared with that of negative group, which was also recovered after two weeks from the drug administration. These results suggested that DW-166HC-I may not cause any chromosomal damage but DW-166HC has in vivo mutagenic potential because of its radioactivity.