• 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.

• Preventive Nutrition and Food Science
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• v.1 no.1
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• pp.64-68
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• 1996

Chromosomal aberration tests in vitro using Chinese hamster lung(CHL) cells were carried out to evaluate the possible role of the MeOH extract of Ecklonia stolonifera in modulating the chromosomal damage induced by Mitomycin C(MMC) and Benzo(a)pyrene(B(a)P), respectively. The MeOH extract of Ecklonia stolonifera(260$\mu\textrm{g}$/ml) reduced significantly the incidence of chromosomal aberration induced by treatment with B(a)P by 80%. The suppressive effect was much stronger than that of $\beta$-carotene, which is well known antimu-tagen. However, there was no marked decrease in the chromosomal aberration induced by MMC. In the tests involving chromosomal aberration induced by the treatment of the MeOH extract of Exklonia stlolnifera alone, there was no significant increase in comparison with the negative control. The results would seem to indicate that. at least under the conditions examined, the MeOH extract of Ecklonis stolonifera decreased the chromosomal aberrations induced by B(a)P in the CHL cells, but had little effect on the chromosomal aberration induced by MMC.

• Molecular & Cellular Toxicology
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• v.5 no.2
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• pp.126-132
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• 2009

The usage and types of chemicals are advancing, specializing, large-scaled increasing, and new chemical exposed workers are concerning to occupational disease. The generation of reactive oxygen in the body from carcinogen, mutation and DNA damage in cancer is protected by natural antioxidants (phytochemicals) with antimutagenic effect. There were many reports of ginsenoside Rb$_1$, Rg$_1$ grievances of the genetic mutation to suppress the effect confirm the genetic toxicity test with chromosomal aberration test and the Comet (SCGE) assay confirmed the suppression effect occurring chromosomal DNA damage. We had wanted to evaluate the compatibility and sensitivity between the chromosomal aberration (CA) test and the Comet assay. We used the CA test and Comet assay to evaluate the anti-genotoxicity of ginsenoside Rb$_1$ and Rg$_1$, in CHO-K1 (Chinese hamster ovary fibroblast) cell in vitro, composed negative control (solvent), positive control (benzo[a]pyrene), test group (carcinogen+variety concentration of ginsenoside) group. The positive control was benzo[a]pyrene (50 $\mu$M), well-known carcinogen, and the negative control was the 1 % DMSO solvent. The test group was a variety concentration of ginsenoside Rb$_1$, Rg$_1$ with 10$^{-8}$%, 10$^{-6}$%, 10$^{-4}$%, 10$^{-2}$%, 1%, 10%. In chromo-somal aberration test, we measured the number of cells with abnormally structured chromosome. In Comet assay, the Olive tail moment (OTM) and Tail length (TL) values were measured. The ratio of cell proliferation was increased 8.3% in 10$^{-8}$%, 10$^{-6}$%, 10$^{-4}$%, 10$^{-2}$%, 1%, 10% Rb$_1$ treated groups, and increased 10.4% in 10$^{-10}$%, 10$^{-8}$%, 10$^{-6}$%, 10$^{-4}$%, 10$^{-2}$%, 1% Rg$_1$ treated groups. In the CA test, the number of chromosomal aberration was decreased all the Rb$_1$ and Rg$_1$ treated groups. In the Comet assay, the OTM values were decreased in all the Rb$_1$ and Rg$_1$ treated groups. To evaluate the compatibility between CA and Comet assay, we compared the reducing ratio of chromosomal abnormalities with its OTM values, it was identified the antimutagenicity of ginsenoside, but it was more sensitive the CA test than the Comet assay. Ginsenoside Rb$_1$ and Rg$_1$ significantly decrease the number of cells with chromosomal aberration, and decrease the extent of DNA migration. Therefore, ginsenoside Rb$_1$, Rg$_1$ are thought as an antioxidant phytochemicals to protect mutagenicity. The in vitro Comet assay seems to be less sensitive than the in vitro chromosomal aberration test.

• Environmental Mutagens and Carcinogens
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• v.21 no.2
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• pp.99-105
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• 2001

Sophoricoside was isolated as the inhibitor of IL-5 bioactivity from Sophora japonica (Leguminosae). It has been reported to has an anti-inflammatory effect on rat paw edema model. To develope as an anti-allergic drug, genotoxicity of sophoricoside was investigated in bacterial and mammalian cell system such as Ames bacterial reversion test, chromosomal aberration assay and single cell gel electrophoresis (Comet) assay. As results, in the range of 1,250~40 $\mu\textrm{g}$/plate sophoricoside concentrations was not shown significant mutagenic effects in Salmonella typhimurium TA 98, TA 100, TA 1535 and TA 1537 strains in Ames test. The 80% cell growth inhibition concentration (IC/SUB 80/) of sophoricoside was determined as above 5,000 $\mu\textrm{g}$/$m\ell$ in Chinese hamster lung (CHL) fibroblast cell and L5178Y mouse lymphoma cell line for the chromosomal aberration and comet assay, respectively. Sophoricoside was not induced chromosomal aberration in CHL fibroblast cell at concentrations of 700, 350 and 175 $\mu\textrm{g}$/$m\ell$ or 600, 300 and 150 $\mu\textrm{g}$/$m\ell$ in the absence or presence of S-9 metabolic activation system, respectively. Also, in the comet assay, the induction of DNA damage was not observed in L5178Y mouse lymphoma cell line both in the absence or presence of S-9 metabolic activation system. From these results, no genotoxic effects of sophoricoside were observed in bacterial and mammalian cell systems used in these experiments.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1501-1506
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• 2015

Gemcitabine is an anti-cancer drug with clinically uses in the treatment of various neoplasms, including breast, ovarian, non-small cell lung, pancreaticand cervical cancers, T-cell malignancies, germ cell tumours, and hepatocellular carcinomas. However, it has also been reported to have many adverse effects. Naturally occurring anti-mutagenic effects, especially those of plant origin, have recently become a subject of intensive research. The present study was therefore designed to investigate the anti-mutagenic effects of Salvia merjamie (Family: Lamiaceae) plant extracts against the mutagenic effects of gemcitabine. The anti-mutagenic properties of Salvia merjamie were tested in Inbred SWR/J male and female mice bone marrow cells. The mice were treated in four groups; a control group treated with 30 mg/kg body weight gemcitabine and three treatment groups, each with 30 mg/kg body weight gemcitabine together with, respectively, 50, 100 and 150 mg/kg body weight Salvia merjamie extract. Chromosomal aberration and mitotic index assays were performed with the results demonstrating that Salvia merjamie extract protects bone marrow cells in mice against gemcitabine induced mutagenicity. This information can be used for the development of a potential therapeutic anti-mutagenic agents.

• Journal of Environmental Health Sciences
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• v.23 no.4
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• pp.9-15
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• 1997

This experiment was carried out to examine the roles of selenium in arsenic- and chromium-induced oxidative stress, which results in chromosomal damage, such as sister chromatid exchange (SCE) and chromosomal aberration (CA). For this purpose, the frequency of CA and SCE related to the level of 0xidative stress were analyzed. Selenium decreased the frequency of CA induced by As. In order to evaluate the effect of selenium on clastogenic factors, media from As- and Cr-treated cells were ultrafiltered and added again to cells in the presence or absence of selenium. Selenium decreased the frequency of SCE by As and Cr. This observation indicates the possibility of presence of clastogenic factor. In addition, the clastogenic factor would be involed in oxidative stress since selenium decreased the level of oxidative stress. Thus, it is suggested that selenium may play a role as an anti-clastogenic effector by preventing the oxidative stress, thereby decreasing the frequency of Asand Cr-induced chromosomal damage.

• Molecular & Cellular Toxicology
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• v.1 no.3
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• pp.179-188
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• 2005

To develop the novel anti-allergic drug, many sophoricoside derivatives were synthesized. Among these derivatives, JSH-II-3, VI-3, VII-3, VIII-3, VII-20 and VII-20 (sodium salt) were selected and subjected to high throughput toxicity screening (HTTS) because they revealed strong IL-5 inhibitory activity and limitation of quantity. Single cell gel electrophoresis (Comet) assay, mouse lymphoma thymidine kinase ($tk^{+/-}$) gene assay (MOLY), chromosomal aberration assay in mammalian cells and Ames reverse mutation assay in bacterial system were used as simplified, inexpensive, short-term in vitro screening tests in our laboratory. Through the primary screening using the comet assay, we could choose the first candidates of sophoricoside derivatives with no genotoxic potentials as JSH-VI-3, VII-3, VII-20 and VII-20 (sodium salt). Also JSH-VII-3, VII-20 and VII-20 (sodium salt) are non-mutagenic in MOLY assay, while JSH-II-3 is mutagenic at high concentration with the presence of metabolic activation system in both comet assay and MOLY assay. The selected derivatives (JSH-VI-3, VII-3, VII-20 and VII-20 (sodium salt) are not mutagenic in S. typhimurium TA98 and TA100 strains both in the presence and absence of metabolic activation. From results of chromosomal aberration assay, 6 h treatment of JSH-VI-3, VII-3 and VII-20 (sodium salt) were not revealed clastogenicity both in the presence and absence of S-9 mixture. Therefore, we suggests that JSH-VI-3, VII-3, VII-20 and VII-20 (sodium salt), as the optimal candidates with both no genotoxic potential and IL-5 inhibitory effects must be chosen. To process the development into new anti-inflammatory drug of these derivatives, further investigation will need.

• Toxicological Research
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• v.30 no.3
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• pp.211-220
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• 2014

Resveratrol has received considerable attention as a polyphenol with various biological effects such as anti-inflammatory, anti-oxidant, anti-mutagenic, anti-carcinogenic, and cardioprotective properties. As part of the overall safety assessment of HS-1793, a novel resveratrol analogue free from the restriction of metabolic instability and the high dose requirement of resveratrol, we assessed genotoxicity in three in vitro assays: a bacterial mutation assay, a comet assay, and a chromosomal aberration assay. In the bacterial reverse mutation assay, HS-1793 did not increase revertant colony numbers in S. typhimurium strains (TA98, TA100, TA1535 and TA1537) or an E. coli strain (WP2 uvrA) regardless of metabolic activation. HS-1793 showed no evidence of genotoxic activity such as DNA damage on L5178Y $Tk^{+/-}$ mouse lymphoma cells with or without the S9 mix in the in vitro comet assay. No statistically significant differences in the incidence of chromosomal aberrations following HS-1793 treatment was observed on Chinese hamster lung cells exposed with or without the S9 mix. These results provide additional evidence that HS-1793 is non-genotoxic at the dose tested in three standard tests and further supports the generally recognized as safe determination of HS-1793 during early drug development.

• 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.