• 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.

• The Korean Journal of Zoology
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• v.20 no.1
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• pp.19-28
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• 1977

In order to evaluate the mutagenic potential in animal for these pesticides which were proved to be mutagenic in the bacterial screening system with a metabolic activation in vitro, we have studied in vivo cytogenetic effects on mouse bone marrow by means of the micronucleus test. The clastogenic activity of the chemical is evaluated as the frequency of micronuclei in polychromatic erythrocytes. We have tested six pesticides, insecticides, DDVP and trichlorfon, fungicide, TMTD, herbicides, NIP and MO and growth regula색, maleic hydrazide. It was found that among the tested pesticides only TMTD exhibited minimal activity in inducing micronuclei. Organophosphorus insecticide DDVP that is the most broadly used and economically important chemical, did not increase the micronuclei frequencies in mouse bone marrow cells as with the all other pesticides tested.

• Environmental Mutagens and Carcinogens
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• v.18 no.2
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• pp.123-128
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• 1998

To evaluate the genotoxicity of SKP-450, an antihypertensive agent the in vitro reverse mutation assay using Salmonella typhimurium, the Chromosome aberration assay using Chinese hamster lung (CHL) cells and the in vivo micronucleus assay using bone marrow cells of ddY mice were performed. In the Reverse mutation test, SKP-450 did not induced mutagenicity in Salmonella typhimurium TA 98, TA 100, TA 1535 and TA 1537 with and without metabolic activation. In the chromosome aberration assay using CHL cells, there was no increased incidence of structural and numerical aberrations with and without metabolic activation. The in vivo induction of micronuclei was measured in polychromatic erythrocytes of bone marrow of male ddY mice at 30 hours after treatment with SKP-450 by p.o once. The results showed no increased incidence of micronucleated polychromatic erythrocytes in bone marrow of ddY male mice treated with SKP-450.

• Toxicological Research
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• v.17 no.3
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• pp.235-239
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• 2001

CJ-50005 is an inactivated whole virus vaccine derived from hepatitis A virus (HM175) grown in human MRC-5 diploid fibroblasts cell culture. In order to evaluate the mutagenic potential of CJ-50005, : 3 sets of mutagenicity tests were performed. In the reverse mutation test wing Salmonella typhimurium TA1535, TA1 537, TA98, TA100 and TA102, CJ-50005 did not increase the number of revertants at any concentration tested in this study (2.8, 1.4, 0.7, 0.35 and 0.175 $\mu\textrm{g}$/plate). CJ-50005, at concentration of 2.8, 1.4 and 0.7 $\mu\textrm{g}$/ml, did not increase the number of cells having structural or numerical chromosome aberration in cytogenic test using Chinese Hamster Lung cells. In mouse micronucleus test, no significant increase in the occurrence of micronucleated polychromatic erythrocytes was observed in ICR male and female mice intraperitoneally administered with CJ-50005 at the doses of 25, 12.5 and 6.25 $\mu\textrm{g}$/kg. These results indicate that CJ-50005 has no mutagenic potential in these in vitro and in vivo system.

• YAKHAK HOEJI
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• v.42 no.4
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• pp.414-421
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• 1998

In order to compare the suppressive effect of quercetin and its glycosides, such as quercitrin (quercetin-3-rhamnoside), isoquercitrin (quercetin-3-glucoside), hyperin (querceti n-3-galactoside)and rutin (quercetin-3-rhamnosyl glucoside), on the genotocicity by benzo(a)pyrene(B(a)P), in vitro sister chromatid exchange(SCE) test using mouse spleen lymphocytes and in vivo micronucleus test using mouse peripheral blood were performed. B(a)P-induced SCEs in vitro were slightly decreased by the simultaneous treatment of quercetin and its glycosides, although there was no significant decrease. On the other hand, MNU induced micronucleated reticulocytes(MNRL7s) in vivo were significantly decreased with a dose-dependent manner in all compounds tested. However, there were no differences between quercetin aglycone and glycosides in the suppressive effects under experimental condition of this study. To elucidate, the action mechanism of quercetin aglycone and its glycosides against B(a)P-induced genotoxicity, the assay of DNA binding with B(a)P was studied. Quercetin aglycone and its glycosides inhibited B(a)P metabolism in the presence of S-9 mix and decreased the B(a)P/DNA binding in the calf thymus DNA with S-9 mix. These results suggest that antigenotoxicity of quercetin antiglycosides on B(a)P-induced genotoxicity is due to decrease of DNA binding with B(a)P through the inhibition of metabolism with B(a)P in the calf thymus DNA. Therefore, quercetin and its glycosides may act as an antigenotoxicity agent and may be useful as a chemopreventive agent of polycyclic aromaic hydrocarbons like B(a)P.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2021.04a
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• pp.67-67
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• 2021

The genus Glycyrrhiza (Licorice) has been used as an oriental herbal medicine for a long time in Asian countries. Wongam (WG), which is Glycyrrhiza new variety, have been developed to improve limitation of licorice including low productivity, environmental restriction and insufficient components by Korea Rural Development Administration. To using WG as a herbal medicine, it is important to reveal the adverse effects in health. In this study, we evaluated the genotoxicity test of WG extract through in vitro bacterial reverse mutation (AMES) assay, in vitro chromosomal aberration assay and in vivo mouse bone marrow micronucleus assay. When compared with the control, WG extract with or without the S9 mix showed no genotoxicity in the AMES assay up to 5000 ㎍/plate and in the chromosomal aberration assay up to 1100 ㎍/ml. In micronucleus assay, no significant increase in the number of micronucleated polychromatic erythrocytes or in the mean ratio of polychromatic to total erythrocytes up to 5000 mg/kg/day for 2 days. The present study demonstrated that WG extract is safe and reliable herbal medicine since no detectable genotoxic effects at least under the conditions of this study.

• Molecular & Cellular Toxicology
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• v.2 no.3
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• pp.176-184
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• 2006

The controversy on genotoxicity of molinate, an herbicide, has been reported in bacterial system, and in vitro and in vivo mammalian systems. To clarify the genotoxicity of molinate, we performed bacterial gene mutation test, in vitro chromosome aberration and mouse lymphoma $tk^{+/-}$ gene assay, and in vivo micronucleus assay using bone marrow cells and peripheral reticulocytes of mice. In bacterial gene mutation assay, no mutagenicity of molinate ($12-185{\mu}g/plate$) was observed in Salmonella typhimurium TA 98, 100, 1535 and 1537 both in the absence and in the presence of S-9 metabolic activation system. The clastogenicity of molinate was observed in the presence ($102.1-408.2\;{\mu}g/mL$) of metabolic activation system in mammalian cell system using Chinese hamster lung fibroblast. However, no clastogenicity was observed in the absence ($13.6-54.3\;{\mu}g/mL$) of metabolic activation system. It is suggested that the genotoxicity of molinate was derived some metabolites by metabolic activation. Molinate was also subjected to mouse lymphoma L5178Y $tk^{+/-}$ cells using microtiter cloning technique. In the absence of S-9 mixture, mutation frequencies (MFs) were revealed $1.4-1.9{\times}10^{-4}$ with no statistical significance. However, MFs in the presence of metabolic activation system revealed $3.2-3.4{\times}10^{-4}$ with statistical significance (p<0.05). In vivo micronucleus (MN) assay using mouse bone marrow cells, molinate revealed genotoxic potential in the dose ranges of 100-398 mg/kg of molinate when administered orally. Molinate also subjected to acridine orange MN assay with mouse peripheral reticulocytes. The frequency of micronucleated reticulocytes (MNRETs) induced 48 hr after i.p. injection at a single dose of 91, 182 and 363 mg/kg of molinate was dose-dependently increased as $10.2{\pm}4.7,\;14.6{\pm}3.9\;and\;28.6{\pm}6.3\;(mean{\pm}SD\;of\;MNRETs/2,000\;reticulocytes)$ with statistical significance (p<0.05), respectively. Consequently, genotoxic potential of molinate was observed in in vitro mammalian mutagenicity systems only in the presence of metabolic activation system and in vivo MN assay using both bone marrow cells and peripheral reticulocytes in the dose ranges used in this experiment. These results suggest that metabolic activation plays a critical role to express the genotoxicity of molinate in in vitro and in vivo mammalian system.

• Environmental Mutagens and Carcinogens
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• v.21 no.1
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• pp.44-50
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• 2001

To identify nongenotoxic carcinogen determined as negative by ICH guideline-recommended standard genotoxicity test battery; Ames test, chromosome aberration assay, mouse lymphoma $tk^{+/-}$ assay, in vivo micronucleus assay, we picked bisphenol A as a model compound. In this study, we applied in vitro BalB/c 3T3 cell transformation assay and Syrian hamster embryo (SHE) cell transfarmation assay. Bisphenol A was treated upto $769.2 ug/m{\ell}$ in BalB/c 3T3 cells and upto $125 ug/m{\ell}$ in SHE cells. bisphenol A didn't induced morphological transformation both with one stage treatment protocol and with two stage treatment protocol. But, treated far 48 hr, Bisphenol A induced morphological transformation significantly in SHE cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.27 no.4
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• pp.745-750
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• 1998

The antimutagenic and antigenotoxic effects of ethanol, methanol, water and non-heating ethanol extract of Ligularia fischeri were investigated using Ames test and micronucleus test. Four solvent extracts by themseleves did not induce mutagenesis. The four extract of 200㎍/plate showed approximately 84.7%, 77.1%, 72.5% and 71% inhibitory effect on the mutagenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) and 67.9%, 66.8%, 64.6% and 56% inhibition on the mutagenesis by 4-nitroquinoline-1-oxide(4NQO) against TA100 strain, whereas 70.2%, 60.9%, 61.9% and 52.8% inhibitions were observed on the mutagenesis induced by 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indol(Trp-P-1) in the presence of 200㎍/plate. TA100 strain was more sensitive than TA98 strain by four kinds of extracts on antimutagenesis. The effects of Ligularia fischeri extracts on the frequencies of micronucleated poly chromatic erythrocytes(MNPECs) induced by MNNG were investigated in the bone marrow. Ten, 20, 40 and 80mg g/kg of each extract were administered to animals immediately after injection of MNNG and the exposure time was 36 hours. Inhibitory effects of Ligularia fischeri ethanol extracts were 12%, 35.3%, 58.8%, and 57%, in the presence of 20, 40, 60 and 80mg/kg, respectively whereas methanol extracts showed 15.5%, 32.7%, 50.8%, and 57.9% inhibitory effects, respectively. Both extracts showed enhanced antimutagenic and antigenotoxic effects. These results showed a good correlation between antimutagenic effects in in vitro and in in vitro assay.

• Toxicological Research
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• v.15 no.1
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• pp.75-78
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• 1999

In order to evaluate the mutagenic potential of Typhoid vaccine, 3 sets of mutagenicity tests were performed. In the reverse mutation test using Salmonella typhimurium TA98, TA100, TA1535 and TA1537, Typhoid vaccine did not increase the number of revertant at the doses of 100, 50, 25, 12.5, 6.25 $\mu\textrm{g}$/plate. I n chromosome aberration analysis using CHO cells were not found chromosomal aberration in different concentrations with or without metabolic activation at the doses of 0.25 mg/ml, 0.5mg/ml, 1mg/ml. In mouse micronucleus test, no significant increase in the occurrence of micronucleated polychromatic erythrocytes was observed in ICE male mice intramuscularly administered with Typhoid vaccine at the dosed of 0.1 mg/ml, 0.5 mg/ml, 1mg/ml. These results indicate that Typhoid vaccine gas no mutagenic potential in these in vitro and in vivo systems.