• Journal of Pharmacopuncture
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• v.23 no.4
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• pp.237-246
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• 2020

Objectives: Capsaicin-containing (CP) pharmacopuncture was developed to treat neuropathic pain. This study was conducted to assess the toxicity of CP extract for pharmacopuncture, using a micronucleus test. Methods: First, a dose range finding study was conducted. Then an in vivo micronucleus test was performed to determine the induction of micronuclei in mouse bone marrow cells after intramuscular administration of CP twice with a 24-hour interval to 8-week-old ICR mice. A high dose of 0.2 mL/animal was selected, and this was sequentially diluted by applying a geometric ratio of 2 to produce two lower dose levels (0.1 and 0.05 mL/animal). In addition, negative and positive control groups were set up, and an HPLC analysis was conducted to confirm the capsaicin content of CP. Results: The incidence of micro-nucleated polychromatic erythrocytes in polychromatic erythrocytes in the CP-treated group was similar to that in the negative-control group, while that in the positive-control group was significantly greater. In addition, the ratio of polychromatic erythrocytes to total erythrocytes in the CP treatment group and the positive control group was not significantly different from the negative control group. In the HPLC analysis, capsaicin in the CP was identified through a comparison with the retention time of the capsaicin standard of 27 min. Conclusion: CP did not show any indication of any potential to induce micronuclei formation in bone marrow cells of ICR mice under the conditions of this study. Further toxicity studies are necessary to ensure the safety of the use of CP in clinical practice.

• Environmental Mutagens and Carcinogens
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• v.24 no.2
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• pp.91-98
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• 2004

Although 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) is a powerful carcinogen in several species, limited model system exist to study carcinogenicity of this compound at cellular level. To enhance our under-standing of carcinogenicity of TCDD at cellular level, we investigated micronucleus (MN) frequency as a index of genetic toxicity and whether TCDD can transform the human cells in culture. Normal human cell lines, skin keratinocyte HaCaT, Chang liver and breast MCF10A cells were used. TCDD did not affect the cell viability of the Chang liver, HaCaT and MCF10A cells. The frequency of micronucleus was increased after treatment of TCDD for 24hr in Chang liver and HaCaT cells, but not changed in MCF10A cells. And we observed putative transformed cells in Chang liver cells exposed to 1 $\mu$M TCDD for 2 weeks. The putative transformed cells were also observed in HaCaT cells with subsequent exposure to TCDD (0.1, 1, 10, 100 nM) for 2 weeks after initial exposure to MNNG, but not observed in MCF10A cells. Collectively, these results indicate that the ability of TCDD to induce micronuclei may be involved in cellular transformation of Chang liver and HaCaT cells. Our putative TCDD-transformed cells of Chang liver and HaCaT are expected to provide a clue to the elucidation of TCDD-induced transformation pathway.

• Environmental Mutagens and Carcinogens
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• v.22 no.4
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• pp.289-295
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• 2002

This study was conducted to quantify of micronucleus frequencies in human umbilical cord blood by supravital staining method with acridine orange, and to find some factors that affected on micronucleus frequncies in humans. In this study, we used umbilical cord blood of new born infants that have sufficient reticulocytes compared with adult peripheral blood. The cord bloods were taken after childbirth from 60 normal infants in industrial and coastal region in Korea. The total of 3 ${mu}ell$ cord blood was applied to slide coated with acridine orange, and micronuclei were observed under fluorescent microscopy. Demographic factors and independent variables were collected from mothers by questionnaire. The frequencies of micronuclei in umbilical cord blood of new born infants were 0-5 per 2,000 reticulocytes by supravital staining method, and mean value and standard deviation were 1.75$\pm$0.97. There were no significant difference by the regions, smoking habits of father or mother. However, age of mother showed significant positive correlation with frequencies of micronuclei (p<0.05). Smoking at home by fathers also was found as a significant variable by muliple regression analysis. Therefore, further studies would be needed for genotoxicological evaluation of new born infants by microneuli test using supravital staining method.

• Journal of Food Hygiene and Safety
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• v.27 no.2
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• pp.141-145
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• 2012

Zizyphi spinosi semen (Z. spinosi) has been used in traditional Chinese medicine for the treatment of rheumatoid arthritis and wounds. However, toxicity in high doses was often observed due to the presence of alkaloids. This study was conducted to investigate the potential genotoxicity of Z. spinosi in vitro and in vivo. This was examined by the Bacterial reverse mutation (Ames) test using Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2uvrA, Chromosomal aberration was investigated using Chinese hamster lung cells and the micronucleus test using mice. Z. Spinosi did not induce mutagenicity in the Ames test, and it did not produce chromosomal aberration in Chinese hamster lung cells with and without metabolic activation, nor in the micronucleated polychromatic erythrocytes in the bone marrow cells in mice. Based on these results, it is concluded that Z. spinosi does not have mutagenic potential under the conditions examined in each study.

• Safety and Health at Work
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• v.6 no.3
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• pp.184-191
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• 2015

Chemical mutagenicity is a major hazard that is important to workers' health. Despite the use of large amounts of allyl chloride, the available mutagenicity data for this chemical remains controversial. To clarify the mutagenicity of allyl chloride and because a micronucleus (MN) test had not yet been conducted, we screened for MN induction by using male ICR mice bone marrow cells. The test results indicated that this chemical is not mutagenic under the test conditions. In this paper, the regulatory test battery and several assay combinations used to determine the genotoxic potential of chemicals in the workplace have been described. Further application of these assays may prove useful in future development strategies of hazard evaluations of industrial chemicals. This study also should help to improve the testing of this chemical by commonly used mutagenicity testing methods and investigations on the underlying mechanisms and could be applicable for workers' health.

• Toxicological Research
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• v.18 no.4
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• pp.349-354
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• 2002

Inflammatory bowel disease (IBD) is a multifactorial disorder with unknown etiology and pathogenesis. Eupatilin, a kind of flavonoids, has been known to be effective for chronic diarrhea in Korea. In this study, we have investigated the genotoxicity of DA-6034, a new synthetic derivative of Eupatilin, wing in vitro and in viuo system such as Ames reverse mutation test, chromosomal aberration test and micronucleus test. in Ames reverse mutation test, DA-6034 treatment at the dose range up to 5,000 $\mu\textrm{g}$/ plate did not induced mutagenicity in Salmonella typhimurium TA98, TA100, TA102, TA1535, TA1537 with and without metabolic activation. Any significant aberration wasn't observed in chinese hamster lung(CHL) fibroblast cells treated with DA-6034 at the concentration of 5, 2.5, 1.25 mg/ml both in the absence and presence of metabolic activation system. In mouse micronucleus test, no significant increase in the occurrence of micronucleated polychromatic erythrocytes was observed in ICR male mice orally administered with DA-6034 of the doses of 2.0, 1.0, 0.5 g/kg. These results indicate that DA-6034 has no mutagenic potential under the condition in this study.

• Journal of Food Hygiene and Safety
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• v.11 no.4
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• pp.299-306
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• 1996

6-[(N-3,4-Dibromophenyl)amino]-7-chloro-5,8-quinolinedione(FCK13) was tested for antifungal activities. The MIC values were determined by the two-fold dilution method. The therapeutic potential of RCK13 had been assessed in comparison with ketoconazole and fluconazole against systemic infections with candida albicans in normal mice. RCK13 had ED50,0.80$\pm$0.21 mg/kg but ketoconazole had ED50, 8.00$\pm$0.73 mg/kg respectively. And administered RCK13 at the ED50 for 14 days improved survival rates as well as ketoconazole. Acute oral toxicity studies of RCK13 were carried out in ICR mice of both sexes. These acute oral toxicities of RCK13 were low and LD50 values were over 2,850 mg/kg in ICR mice. The genotoxicities of RCK13 had been evaluated. RCK13 was negative in Ames test with Salmonella typhimurium and chromosomal aberration test in CHL cells. The clastogenicity was tested on the RCK13 with in vivo mouse micronucleus assay. RCK13 did not show any clastogenic effect in mouse peripheral blood and was negative in mouse micronucleus assay. These results indicate that RCK13 has no genotoxic potential under these experimental conditions.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3343-3347
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• 2012

The aim of this study was to investigate the anticlastogenicity as well as the clastogenicity of Eryngium foetidum leaf (EF) using the in vivo mouse peripheral blood erythrocyte micronucleus assay. Eighty ICR male mice were fed AIN-76 diet supplemented with ground freeze-dried EF at 0.0%, 0.8%, 1.6% and 3.2% for 2 weeks prior to the administration of both direct-acting, mitomycin C (MMC), and indirect-acting, 7, 12-dimethylbenz(a) anthracene (DMBA) clastogens. Peripheral blood samples were collected from mice just before administration of clastogen and at 24 and 48 h thereafter for MMC. Blood samples were collected at the same times and after 72 h for DMBA. Then, reticulocytes in blood samples were counted using fluorescent microscopy. The results indicated that EF had no clastogenic effect in mice. All doses of diets supplemented with EF decreased the number of micronucleated peripheral reticulocytes in all the MMC-treated groups in a dose dependent manner, but significant reduction was found only at 1.6% and 3.2% EF in the DMBA-treated groups. It can be concluded that EF has no clastogenicity, but possesses anticlastogenic potential against both direct- and indirect-acting types of clastogen in mice.

• Toxicological Research
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• v.29 no.4
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• pp.249-255
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• 2013

Erythritol is a sugar alcohol that is widely used as a natural sugar substitute. Thus, the safety of its usage is very important. In the present study, short-term genotoxicity assays were conducted to evaluate the potential genotoxic effects of erythritol. According to the OECD test guidelines, the maximum test dose was 5,000 ${\mu}g$/plate in bacterial reverse mutation tests, 5,000 ${\mu}g/ml$ in cell-based assays, and 5,000 mg/kg for in vivo testing. An Ames test did not reveal any positive results. No clastogenicity was observed in a chromosomal aberration test with CHL cells or an in vitro micronucleus test with L5178Y $tk^{+/-}$ cells. Erythritol induced a marginal increase of DNA damage at two high doses by 24 hr of exposure in a comet assay using L5178Y $tk^{+/-}$ cells. Additionally, in vivo micronucleus tests clearly demonstrated that oral administration of erythritol did not induce micronuclei formation of the bone marrow cells of male ICR mice. Taken together, our results indicate that erythritol is not mutagenic to bacterial cells and does not cause chromosomal damage in mammalian cells either in vitro or in vivo.

• Journal of Food Hygiene and Safety
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• v.14 no.1
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• pp.55-59
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• 1999

6-(4-Iodophenyl)amino-7-chloro-5,8-quinolinedione (RCK9) was evaluated for antifungal activities. The MIC values of RCK9 were determined against A. flavus, c. albicans, C. neoformans and F. oxysporium. The RCK9 showed generally potent antifungal activities against the tested fungi. Acute oral toxicity studies of RCK9 were carried out in ICR mice of both sexes. These acute oral toxicities of RCK9 had been evaluated. RCK9 were low and LD50 values were over 2,850 mg/kg in ICR mice. The genotoxicities of RCK9 had been evaluated. RCK9 was negative in Ames test with Salmonella typhimurium and chromosomal aberration test in CHL cells. The clastogenicity was tested on the RCK9 with in vivo mouse micronucleus assay. RCK9 did not show any clastogenic effect in mouse peripheral blood and was negative in mouse micronucleus assay. The results indicate that RCK9 has no genotoxic potential under these experimental conditions.