• Environmental Mutagens and Carcinogens
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• v.24 no.2
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• pp.99-107
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• 2004

The validation of many synthetic chemicals that may pose a genetic hazard in our environment is of great concern at present. Since these substances are not limited to the original products, and enter the environment, they have become widespread environmental pollutants, thus leading to a variety of chemicals that possibly threaten the public health. In this respect, the regulation and evaluation of the chemical hazard playa very important role to environment and human health. The clastogenicity of 11 synthetic chemicals was evaluated in Chinese hamster lung (CHL) fibroblast in vitro. Benzoyl chloride (CAS No. 98-88-4) induced chromosomal aberrations with statistical significance at the concentration of 31-123 $\mug/ml$ and 43 $\mug/ml$ in the absence and presence of S-9 metabolic activation system, respectively. 2-Propyn-l-o1 (CAS No. 107-19-7) and 2-Phenoxy ethanol (CAS No. 122-99-6) revealed clastogenicity only at the highest concentration in the presence of S-9 mixture. However, 1-naphthol (CAS No. 90-15-3) which is one of the most cytotoxic chemical among 11 chemicals tested revealed no clastogenicity both in the presence and absence of S-9 metabolic activation system. From the results of chromosomal aberration assay with 11 synthetic chemicals in CHL fibroblast in vitro, Benzoyl chloride (CAS No. 98-88-4), 2-Propyn-l-01 (CAS No. 107-19-7) and 2-Phenoxy ethanol (CAS No. 122-99-6) revealed positive clastogenic results in this study.

• Environmental Mutagens and Carcinogens
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• v.22 no.4
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• pp.215-222
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• 2002

The detection of many synthetic chemicals used in industry that may pose a genetic hazard in our environment is of great concern at present. Since these substances are not limited to the original products, and enter the environment, they have become widespread environmental pollutants, thus leading to a variety of chemicals that possibly threaten the public health. In this respect, to regulate and to evaluate the chemical hazard will be important to environment and human health. The clastogenicity of 17 synthetic chemicals was evaluated in Chinese hamster lung fibroblast cells in vitro. Two most cytotoxic chemicals, dodecyl methacrylate (CAS No. 142-90-5) and 2-ethylhexyl methacrylate (CAS No. 688-84-6), among 17 chemicals tested revealed no clastogenicity in the range of 0.0165-0.066 $\mu\textrm{g}$/$m\ell$ and 0.006-0.024 $\mu\textrm{g}$/$m\ell$ both in the presence and absence of metabolic activation system, respectively. All 17 chemicals revealed no significant induction of chromosomal aberration both in the presence and absence of metabolic activation system in this assay. From the results of chromosomal aberration assay with 17 synthetic chemicals in Chinese hamster lung cells in vitro, we did not observed positive clastogenic results in this study.

• Toxicological Research
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• v.30 no.2
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• pp.131-138
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• 2014

Radix Astragali, the root of Astragalus (A.) membranaceus, has been applied in a variety of diseases for a long time in Asian countries such as Korea and China. In addition, the aerial parts such as leaves and stems of A. membranaceus have received a great deal of attention. Recently, the polysaccharide fraction showing a potent immunomoduating activity was isolated from the aerial parts of A. membranaceus. Thus, the aerial parts of A. membranaceus would be worthy enough for a food material and a dietary supplement. However, they should be safe even though valuable. In our previous study, it was estimated that NOAEL for female rats are 5000 mg/kg/day of the crude polysaccharide fraction from A. membranaceus-aboveground parts. As a series of safety evaluation, genotoxicity test for the crude polysaccharide fraction was carried out in this study. In conclusion, the three genotoxicity assays provided strong overall support that the crude polysaccharide fraction lacks mutagenic and/or clastogenic potential under the GLP-based test conditions. This indicates the aerial parts of A. membranaceus would be safe enough for a food material and a dietary supplement.

• Toxicological Research
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• v.30 no.2
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• pp.121-130
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• 2014

The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions.

• Toxicological Research
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• v.24 no.4
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• pp.321-328
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• 2008

Smoke flavors based on the thermal decomposition of wood have been applied to a variety of food products as an alternative for traditional smoking. Despite its increasing use, the available genotoxicity data on wood smoke flavors (WSF) are still controversial. Thus, potential genotoxic effects of WSF in four short-term in vitro genotoxicity assays were investigated, which included the Ames assay, chromosomal aberration assay, micronucleus test and the alkaline comet assay. WSF did not cause any mutation in the Ames assay using five tester strains at six concentrations of 0.16, 0.31, 0.63, 1.25, 2.5 and 5 ${\mu}l/plate$. To assess clastogenic effect, the in vitro chromosomal aberration assay was performed using Chinese hamster lung cells. No statistically significant increase in the number of metaphases with structural aberrations was observed at the concentrations of 1.25, 2.5, and 5 ${\mu}l/ml$. The in vitro comet assay and micronucleus test results obtained on L5178Y cells also revealed that WSF has no genotoxicity potential, although there was a marginal increase in micronuclei frequencies and DNA damage in the respective micronucleus and comet assays. Taken together, based on the results obtained from these four in vitro studies, it is concluded that WSF is not a mutagenic agent in bacterial cells and causes no chromosomal and DNA damage in mammalian cells in vitro.

• 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.

• Nutritional Sciences
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• v.9 no.3
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• pp.212-226
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• 2006

The involvement of arachidonic acid (AA) metabolizing enzyme, lipoxygenase (LOX), in the development of particular tumors in humans has gradually been acknowledged and LOX has emerged as a novel target to prevent or treat human cancers. In the mouse skin carcinogenesis model, which provides an excellent model to study multistage nature of human cancer development, many studies have shown that some of the LOXs are constitutively upregulated in their expression. Moreover, application of LOX inhibitors effectively reduced tumor burdens, which implicates the involvement of LOX in mouse skin tumor development as well. 8S-LOX is a recently cloned LOX, which is specifically expressed in mouse skin after 12-O-tetradecanoyl-phorbol-13-acetate (TPA) treatment but not in normal skin. Unlike other members of the LOX 'family' expressed in mouse skin, this TPA-induced expression of 8S-LOX is prominent only in the skin of the TPA tumor promotion-sensitive strains of mice (SENCAR, CD-1, and NMRI) but not in the promotion-resistant C57BL/6J mice. This is a very unique phenomenon among strains of mice. Constitutive upregulation of 8S-LOX was also found in early stage papillomas and the expression was gradually reduced as the tumors became malignant. Based on these observations, it has been thought that 8S-LOX is involved in TPA-induced tumor promotion as well as in tumor conversion from papillomas to carcinomas. In accordance with this hypothesis, several studies have suggested possible roles of 8S-hydroxyeicosatetraenoic acid (HETE), an AA metabolite of 8S-LOX, in mouse skin tumor development. A clastogenic activity of 8S-HETE was demonstrated in primary keratinocytes and a close correlation between the levels of etheno-DNA adducts and 8S-HETE during skin carcinogenesis was also reported. On the other hand, it has been reported that 8S-LOX protein expression is restricted to a differentiated keratinocyte compartment Moreover, reported findings on the ability of 8S-HETE to cause keratinocyte differentiation appear to be contrary to the procarcinogenic features of the 8S-LOX expression, presenting a question as to the role of 8S-LOX during mouse skin carcinogenesis. In this review, molecular and biological features of 8S-LOX as well as current views on the functional role of 8S-LOX/8S-HETE during mouse skin carcinogenesis are presented.

• YAKHAK HOEJI
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• v.42 no.5
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• pp.527-533
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• 1998

6-(3,4-Dichlorophenyl)amino-7-chloro-5,8-quinolinedione (RCK50) was tested for antifungal activities in mice systemically infected with Candida albicans. The therapeutic potential of RCK50 was also assessed in comparison with ketoconazole. CK50 had $ED_{50}$ 0.22${\pm}$0.01mg/kg. Ketoconazole as a positive control had $ED_{50}$ 6.00${\pm}$1.70mg/kg. Intraperitoneally administered RCK50 at the $ED_{50}$ for 7 days and 14 days reduced Candida albicans colony count in the kidneys and liver. And administered RCK50 at the $ED_{50}$ for 14 days improved survival rates. The genotoxicities of RCK50 had been evaluated. RCK50 was negative in Ames test with Salmonella typhimurium and chromosomal aberration test in CHL cells. RCK50 did not show any clastogenic effect in mouse peripheral blood and was negative in mouse micronucleus assay. These results indicate that RCK50 has no genotoxic potential under these experimental conditions. Acute oral toxicity studies of RCK50 were carried out in ICR mice of both sexes. RCK50 did not show acute oral toxicities and $LD_{50}$ values were over 2,850mg/kg in ICR mice.

• Journal of Korean Medicine Rehabilitation
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• v.31 no.1
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• pp.59-79
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• 2021

Objectives This study was performed to observe the genotoxic effect of the ChondroT. Methods To evaluate the genotoxicity of ChondroT, an experiment of bacterial reverse mutation test, in vitro mammalian chromosomal aberration test and mammalian erythrocyte micronucleus test in mouse was conducted. Results TA98, TA100 and TA1537 strains in the absence of metabolic activation system (S9 mix), the number of revertant colonies being greater than 2-fold of the respective negative control value. Both in -S9 mix and +S9 mix, the frequencies of aberration cells with structural aberration and numerical aberrations of chromosome were less than 5%. There was no increase of polychromatic erythrocyte with one or more micronuclei at any dose of test substance compared to the negative control group (p<0.05). Conclusions In TA98, TA100 and TA1537 strains in the absence of metabolic activation system (S9 mix), the number of revertant colonies was greater than 2-fold of the respective negative control value, showing positive results. ChondroT was considered to be non-clastogenic to Chinese hamster lung (CHL/IU) cells under the present experimental condition. and ChondroT was determined not to induce an increased frequency of micronuclei in the bone marrow cells of male ICR mice under the present experimental condition.

• Environmental Mutagens and Carcinogens
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• v.18 no.2
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• pp.71-76
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• 1998

Exposure to environmental toxicants can cause cellular problems including the interference of DNA repair processes which may lead to the development of cancer. The existence of toxicant-induced DNA repair abnormality was investigated using mice exposed in vivo to genotoxic chemicals and then challenging their exposed lymphocytes in vitro with bleomycin. The repair of bleomycin-induced DNA damage as estimated by the frequency of chromosome aberrations was determined. Our data indicates that the observed aberration frequencies after in vivo exposure to N-methyl-N'-nitro-N-nitnsoguanidine (MNNG) and in vitro challenge with bleomycin are consistently higher than expected. The enhanced response is not due to the induction of chromosome damage by 25 or 50 mg/kg MNNG since the chemical did not cause chromosome aberrations in lymphocytes of these mice. The observed response after the combined exposure to benzo[a]pyrene (BP) and bleomycin was significantly lower than expected with low in vivo doses of BP (50 mg/kg) and then significantly higher than expected with the high doses (200 mg/kg). We interpret our data to indicate that in vivo exposure to genotoxic agents can cause abnormal DNA repair activities. The response is, however, independent of the clastogenic activities of the inducing chemicals, but dependent upon the inducing agents and on the exposure doses.