• Toxicological Research
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• v.18 no.1
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• pp.79-85
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• 2002

YHB216 is one of new recombinant human erythropoietins (rHu-EPO) developed by Yuhan Research Institute. The rHu-EPO products are widely being used for the treatment of various types of anemia. As a series of safety studies on YHB216, we performed the local irritation test (dermal & ocular application) in male New Zealand White rabbits and micronucleus test in male ICR mice. In the skin irritation test, 0.5 ml of YHB216 10,000 IU/ml solution was applied to the back skin of rabbits for 24 hours and sub-sequent observation was performed. There was no induced response after the treatment and the primary irritation index (P.I.I.) was‘0’. In the eye irritation test, 0.1 ml of YHB216 10,000 IU/mL solution was instilled into the conjunctiva of the eye. No treatment-related reaction was observed at the cornea, iris, and conjunctiva. In the micronucleus test, YHB216 was administered intravenously to male mice (6 mice per group) at dose levels of 0, 6,250, 12,500, and 25,000 IU/kg. Bone marrow cells were collected at 24 hours after the treatment. YHB216 treated groups showed no significant difference in the P/N (polychromatic erythrocyte/ normochromatic erythrocyte) ratio and in the number of micronucleated polychromatic erythrocyte com-pared with the control. In conclusion, YHB216 was found to be a non-irritating material up to 10,000 IU/ml in the local irritation test and to be a non-mutagen up to 25,000 IU/kg in the micronucleus test.

• Journal of Pharmacopuncture
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• v.26 no.4
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• pp.366-372
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• 2023

Objectives: We aimed to evaluate the genotoxicity of a recently developed no-pain pharmacopuncture (NPP) targeting muscle relaxation and analgesia using the micronucleus test. Methods: To evaluate the potential of NPP extracts to induce micronuclei in rat bone marrow cells, a micronucleus test was performed using male Sprague-Dawley rats. The test substance NPP was administered intramuscularly at concentrations of 0.25, 0.5, and 1 mL/animal. Saline was used as the negative control and cyclophosphamide as the positive control. Results: No NPP treatment-related deaths or abnormal changes in general appearance were observed at any dose level during the experimental period. No statistically significant differences in body weight were observed in any of the NPP dose groups compared to the saline negative control group. NPP did not cause a significant increase in the incidence of micronucleated polychromatic erythrocytes (PCEs) and PCEs or in the ratio of PCE-to-total erythrocytes. Conclusion: The NPP extract did not exhibit genotoxic in Sprague-Dawley rat bone marrow cells under the conditions of this study. Further toxicity studies of the NPP extract are required.

• Biomolecules & Therapeutics
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• v.8 no.3
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• pp.248-254
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• 2000

(R)-JG-381, a R form of alkylglycidic acid derivative, was examined for mutagenicity in the reverse mutation test on bacteria, chromosomal aberration test on cultured mammalian cells and micronucleus test in mice. In the reverse mutation test on bacteria using Salmonella typhimurium strain TA98, TA100, TA102, TA1535, TA1537 with or without a metabolic activation system (S9 mix), (R)-JG-381 did not affect the revertant colonies but significantly increased revertant colonies in one test strain, TA98, compared with the vehicle control. In the chromosomal aberration (CA) test using cultured Chinese Hamster Lung fibroblast(CHL) cells, the number of aberrant cells was clot increased in the presence or absence of 59 mix at concentration of the (R)-JG-381 0.025 $\mu$l/m1 to 0.1 $\mu$l/m1, compared with vehicle control. In the micronucleus (MN) test, micronucleated polychromatic erythrocytes in the (R)-JG-381-treated mice were not different from those of the vehicle-treated mice.

• The Journal of Korean Medicine
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• v.42 no.4
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• pp.25-39
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• 2021

Objectives: Ssanghwa-tang (SHT) is a traditional herbal formula comprising nine medicinal herbs, and it is used for reducing fatigue in Korea. SHT exerts various effects such as anti-inflammatory, antioxidant, and anti-aging activities, and protection against acute hepatotoxicity. However, the genotoxicity of SHT has not yet been established. Methods: Ten components were identified in SHT water extract by using high-performance liquid chromatography analysis. We assessed the genotoxicity of SHT by using bacterial reverse mutation (Ames test), chromosome aberration, and in vivo micronucleus tests. Results: The contents of paeoniflorin, glycyrrhizin, and liquiritin apioside in SHT were 15.57, 6.94, and 3.48 mg/g extract, respectively. SHT did not increase the revertant colonies of Salmonella typhimurium and Escherichia coli strains in the presence or absence of metabolic activity. Although SHT did not induce structurally abnormal chromosomes in Chinese hamster lung (CHL) cells in the presence of metabolic activity, the number of structurally aberrated chromosomes increased dose-dependently in the absence of metabolic activity. In the in vivo micronucleus test, SHT did not affect the formation of micronuclei compared with the vehicle control. Conclusions: Genotoxicity of SHT was not observed in the Ames test and in vivo micronucleus test. However, based on the results of chromosome aberration test, it can be presumed that SHT has the potential to induce genotoxicity because it induced structurally abnormal chromosomes in the absence of metabolic activity.

• Toxicological Research
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• v.14 no.2
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• pp.211-216
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• 1998

In order to evaluate the mutagenic potential of SDK(skin decontamination kit) produced by Agency for Defense Development(ADD), were performed Salmonella typhimurium reversion assay, chromosomal aberration test on chinese hamster ovarian cells and in vivo micronucleus assay using mouse bone marrow cells according to the established regulation of Korean Food and Drug Administration. In the reverse mutation test using Salmonella typhimurium TA98, TA100, TA1535 and TA1537 did not in-crease the number of revertant at any of the concentration tested in this study. SDK did not increase the number of cells having structural or numerical chromosome aberration in cytogenetic test. In mouse micronucleus test, no significant increase in the occurrence oj micro nucleated polychromatic erythrocytes were observed in ICR male mice intraperitoneally administered with SDK. These results indicate that SDK has no mutagenic effects under these experimental conditions.

• Toxicological Research
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• v.20 no.2
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• pp.153-158
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• 2004

To evaluate the genotoxicity of CJ-11555, an anti-cirrhotic agent, the reverse mutation test, chromosomal aberration test and in vivo micronucleus test in rats were performed. In the reverse mutation test, the treatment of CJ-11555 at doses of 33.3, 100, 333, 1000, 3330 and 5000 $\mu\textrm{g}$/plate with and without 89 did not induce mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, TA1537, and Escherichia coli (E. call) WP2uvrA. In chromosomal aberration test, CJ-11555 did not induce structural a chromosomal aberration in Chinese hamster ovary (CHO) cells with and without metabolic activation at all doses. In micronucleus test, CJ-11555 did not induce any statistically significant increases in micronucleated polychromatic erythrocyte (MNPCE) at doses of 500, 1000, and 2000 mg/kg. These results suggest that CJ-11555 might not have a mutagenic potential under the conditions in this study.

• Journal of Food Hygiene and Safety
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• v.11 no.1
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• pp.17-24
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• 1996

The genotoxicity of combinations of four p-oxybenzoic acids (methyl paraben, ethyl paraben, isopropyl paraben, butyl paraben) and benzoic acid had been evaluated. The in vitro Ames test using Salmonella typhimurium (TA 98, TA 100, 1535, TA 1537) and the invivo micronucleus assay using mouse peripheral blood were performed. Methyl paraben plus benzoic acid, ethyl paraben plus benzoic acid, and ethl paraben plus butyl paraben slightly increased the frequency of microuncleated reticulocytes in the high doses, but were negative in Ames test with Salmonella typhimurium with and without rat liver microsomal activation. The other combinations tested were negative in Ames test and did not show any clastogenic effect in micronucleus test. These results suggest that genotoxicity can produced by th combination of p-oxybenzoic acid.

• Environmental Mutagens and Carcinogens
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• v.22 no.2
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• pp.106-111
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• 2002

AG6O, the complex of acriflavine and guanosine, has been shown to possess the synergistic antitumorigenic activity in the previous paper (J. Pharm. Pharmacol. 1997, 49:216). In this study, we have investigated the genotoxic properties of AG60 using in vitro and in vivo system such as Ames bacterial reversion test, chromosomal aberration assay and micronucleus assay. In Ames reverse mutation test, AG60 treatment at the dose range up to 250 $\mu\textrm{g}$/plate caused the dose-independent random induction of the mutagenic colony formation in S. typhimurium TA98, TA100, TA1537, and E. coli WP2uvrA, while any mutagenic effect of AG60 wasn't observed in S. typhimurium TA1535. Any significant chromosomal aberration wasn't observed in chinese hamster lung (CHL) fibroblast cells incubated with PBS or AG60 at the concentrations of 2.5, 5, 10 $\mu\textrm{g}$/$m\ell$ for 24 hours without but even with 59 metabolic activation system for 6 hours. In vivo ICR mice, the intramuscular injection of AG60 at the doses of 7.15, 14.3, and 28.6 mg/kg did not induce the frequency of micronucleus formation. However, mitomycin C, as one of the positive controls at the dose of 2 mg/kg caused the 8.4% induction in the frequency of micronucleus and 24% increase in the chromosomal aberration.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2003.10a
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• pp.133-133
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• 2003

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.123-123
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• 1995

To evaluate the genetic toxicity of NP-77A which is selected as the candidate of anti-HBV agent, we performed ames test, micronucleus test, and chromosome aberration test on the CHL cell in vitro. The Ames test was carried out with 5 fold diluted 5 concentrations from 25mg/plate using S. typhimurium and E.coli. After 48hrs incubation, revertant colony numbers was calculated with and without metabolic activation system. In vivo micronucleus test, we investigated the rate of the occurrence of micronucleus after I.P. administration to mice. Andalso, we observed the incidence rate of cells with chromosomal aberration by NP-77A treatment using CHL cell line.