• Environmental Mutagens and Carcinogens
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• v.24 no.1
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• pp.33-39
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• 2004

To validate and to estimate the chemical hazard playa very important role to environment and human health. The detection of many synthetic chemicals including agrochemicals 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. Pyrazosulfuron-ethyl [Ethyl-5-(4,6-dimethoxypyrimidin-2-ylcarbamoylsulfamoyl)-1-methylpyrazole-4-carboxylate, $C_{14}H_{18}N{6}O_{7}S,$ M.W. =414.39, CAS No. 93697-74-6], is one of well known rice herbicide belong in the sulfonyl urea group. To clarify the genotoxicity of this agrochemical, Ames bacterial reversion assay, in vitro chromosomal aberration assay with Chinese hamster lung (CHL) fibroblast and bone marrow micronucleus assay in mice were subjected. In Ames assay, although pyrazosulfuron-ethyl revealed cytotoxic at 5,000-140 $\mug/plate$ in Salmonella typhimurium TA100, no dose-dependent mutagenic potential in 4.4～70 $\mug/plate$ of S. typhimurium TA 98, TA 100, TA1535 and TA 1537 both in the absence and presence of S-9 metabolic activation system was observed. Using CHL fibroblasts, the 50% cell growth inhibition concentration $(IC_{50})$ of pyrazosulfuron-ethyl was determined as 1,243 $\mug/mL,$ and no chromosomal aberration was observed both in the absence and presence of S-9 mixture in the concentration range of 311-1,243 $\mug/mL.$ And also, in vivo micronucleus assay using mouse bone marrow, pyrazosulfuron-ethyl revealed no remarkable induction of MNPCE (micronucleated polychromatic erythrocytes/1000 polychromatic erythrocytes) in the dose range of 625-2,500 mg/kg body weight when administered orally. Consequently, Ames bacterial gene mutation with Salmonella typhimurium, in vitro chromosome aberration with mammalian cells and in vivo bone marrow micronucleus assay revealed no clastogenic potential of pyrazosulfuron-ethyl in this study.

• Archives of Pharmacal Research
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• v.12 no.2
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• pp.94-98
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• 1989

Induction of micronuclei by diesel emission particle extract (DEPE) in mouse bone marrow cells was suppressed by pre-treatment with ascorbic acid, ${\alpha}-tocopherol$ or glutathione (GSH). These compounds were given orally to mice at the dose of 1, 10 or 100 mg/kg/day for 5 consecutive days. The dose of DEPE (200 mg/kg) was administered intraperitoneally once to mice with the 5th administration of test compounds. Ascorbic acid, ${\alpha}-tocopherol$ and GSH all showed the dose-dependent suppression on DEPE-induced micronuclei.

• YAKHAK HOEJI
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• v.36 no.4
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• pp.334-340
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• 1992

Ethanol, total saponin and petroleum ether extract of Panax ginseng C.A. Meyer were tested for their anticlastogenic effects against induction of micronuclei by cyclophosphamide and benzo(a)pyrene in mice. Ginseng petroleum ether extract (GPEE) showed the highest suppressive effect among three extracts. GPEE was also tested to compare their anticlastogenic effect against several well-known carcinogens: such as mitomycin C, 7, 12-dimethyl benzo(a)anthracene, ethyl methane sulfonate, dimethylnitrosamine and busulfan. GPEE showed the anticlastogenic effect against most of carcinogens, although there were no significant effects against 7, 12-dimethyl benzo(a) anthracene, dimethyl nitrosoamine and busulfan-induced micronuclei.

• Environmental Analysis Health and Toxicology
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• v.30
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• pp.14.1-14.7
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• 2015

Objectives Cigarette smoking is associated with carcinogenesis owing to the mutagenic and genotoxic effects of cigarette smoke. The aim of this study was to evaluate the mutagenic and genotoxic effects of Korean cigarettes using in vitro assays. Methods We selected 2 types of cigarettes (TL and TW) as benchmark Korean cigarettes for this study, because they represent the greatest level of nicotine and tar contents among Korean cigarettes. Mutagenic potency was expressed as the number of revertants per ${\mu}g$ of cigarette smoke condensate (CSC) total particulate matter whereas genotoxic potency was expressed as a concentration-dependent induction factor. The CSC was prepared by the International Organization for Standardization 3308 smoking method. CHO-K1 cells were used in vitro micronucleus (MNvit) and comet assays. Two strains of Salmonella typhimurium (Salmonella enterica subsp. enterica ; TA98 and TA1537) were employed in Ames tests. Results All CSCs showed mutagenicity in the TA98 and TA1537 strains. In addition, DNA damage and micronuclei formation were observed in the comet and MNvit assays owing to CSC exposure. The CSC from the 3R4F Kentucky reference (3R4F) cigarette produced the most severe mutagenic and genotoxic potencies, followed by the CSC from the TL cigarette, whereas the CSC from the TW cigarette produced the least severe mutagenic and genotoxic potencies. Conclusions The results of this study suggest that the mutagenic and genotoxic potencies of the TL and TW cigarettes were weaker than those of the 3R4F cigarette. Further study on standardized concepts of toxic equivalents for cigarettes needs to be conducted for more extensive use of in vitro tests.

• Environmental Analysis Health and Toxicology
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• v.28
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• pp.3.1-3.8
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• 2013

Objectives We investigated the genotoxic effects of 40-59 nm silver nanoparticles (Ag-NPs) by bacterial reverse mutation assay (Ames test), in vitro comet assay and micronucleus (MN) assay. In particular, we directly compared the effect of cytochalasin B (cytoB) and rat liver homogenate (S9 mix) in the formation of MN by Ag-NPs. Methods Before testing, we confirmed that Ag-NPs were completely dispersed in the experimental medium by sonication (three times in 1 minute) and filtration ($0.2{\mu}m$ pore size filter), and then we measured their size in a zeta potential analyzer. After that the genotoxicity were measured and especially, S9 mix and with and without cytoB were compared one another in MN assay. Results Ames test using Salmonella typhimurium TA98, TA100, TA1535 and TA1537 strains revealed that Ag-NPs with or without S9 mix did not display a mutagenic effect. The genotoxicity of Ag-NPs was also evaluated in a mammalian cell system using Chinese hamster ovary cells. The results revealed that Ag-NPs stimulated DNA breakage and MN formation with or without S9 mix in a dose-dependent manner (from $0.01{\mu}g/mL$ to $10{\mu}g/mL$). In particular, MN induction was affected by cytoB. Conclusions All of our findings, with the exception of the Ames test results, indicate that Ag-NPs show genotoxic effects in mammalian cell system. In addition, present study suggests the potential error due to use of cytoB in genotoxic test of nanoparticles.

• Molecular & Cellular Toxicology
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• v.3 no.2
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• pp.107-112
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• 2007

o-Nitrotoluene is used to synthesize artificial dyes and raw materials of urethane resin. In this study, we have carried out in vitro genetic toxicity tests and microarray analysis to understand the underlying mechanisms and the mode of action of toxicity of onitrotoluene. TA1535 and TA98 cells were treated with o-nitrotoluene to test its toxicity by basic genetic toxicity test. Ames and two new in vitro micronucleus and COMET assays were applied using CHO cells and L5178Y cells, respectively. In addition, microarray analysis of differentially expressed genes in L5178Y cells in response to o-nitrotoluene was analyzed using Affymatrix genechip. The result of Ames test was that o-nitrotoluene treatment did not increase the mutations both in base substitution strain TA1535 and in frame shift TA98. o-Nitrotoluene has not increased micronuclei in CHO cells. But onitrotoluene increased DNA damage in L5178Y cell. Two-hundred two genes were initially selected as differentially expressed genes in response to o-nitrotoluene by microarray analysis and forty four genes among them were over 2 times of log fold changed. These forty four genes could be candidate biomarkers of genetic toxic action of o-nitrotoluene related to induction of mutation and/or induction of micronuclei and DNA damage. Further confirmation of these candidate markers related to the DNA damage will be useful to understand the detailed mechanism of action of o-nitrotoluene.

• Molecular & Cellular Toxicology
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• v.3 no.2
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• pp.90-97
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• 2007

8-Hydroxyquinoline is used as antibacterial agent and antioxidant based on its function inducing the chelation of ferrous ion present in host resulting in production of chelated complex. This complex being transported to cell membrane of bacteria and fungi exerts antibacterial and antifungal action. In this study, we have carried out in vitro genetic toxicity tests and microarray analysis to understand the underlying mechanisms and the mode of action of toxicity of 8-hydroxyquinoline. TA1535 and TA98 cells were treated with 8-hydroxyquinoline to test its toxicity by basic genetic toxicity test, Ames and two new in vitro micronucleus and COMET assays were applied using CHO cells and L5178Y cells, respectively. In addition, microarray analysis of differentially expressed genes in L5178Y cells in response to 8-hydroxyquinoline were analyzed using Affymatrix genechip. The result of Ames test was that 8-hydroxyquinoline treatment increased the mutations in base substitution strain TA1535 and likewise, 8-hydroxyquinoline also increased mutations in frame shift TA98. 8-Hydroxyquinoline increased micronuclei in CHO cells and DNA damage in L5178Y. 8-Hdroxyquinoline resulted in positive response in all three tests showing its ability to induce not only mutation but also DNA damage. 783 Genes were initially selected as differentially expressed genes in response to 8-hydroxyquinoline by microarray analysis and 34 genes among them were over 4 times of log fold changed. These 34 genes could be candidate biomarkers of genetic toxic action of 8-hydroxyquinoline related to induction of mutation and/or induction of micronuclei and DNA damage. Further confirmation of these candidate markers related to their biological function will be useful to understand the detailed mode of action of 8-hydroxyquinoline.

• Toxicological Research
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• v.34 no.4
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• pp.281-290
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• 2018

Exposure to chemical agents is an inevitable consequence of modern society; some of these agents are hazardous to human health. The effects of chemical carcinogens are of great concern in many countries, and international organizations, such as the World Health Organization, have established guidelines for the regulation of these chemicals. Carcinogens are currently categorized into two classes, genotoxic and non-genotoxic carcinogens, which are subject to different regulatory policies. Genotoxic carcinogens are chemicals that exert carcinogenicity via the induction of mutations. Owing to their DNA interaction properties, there is thought to be no safe exposure threshold or dose. Genotoxic carcinogens are regulated under the assumption that they pose a cancer risk for humans, even at very low doses. In contrast, non-genotoxic carcinogens, which induce cancer through mechanisms other than mutations, such as hormonal effects, cytotoxicity, cell proliferation, or epigenetic changes, are thought to have a safe exposure threshold or dose; thus, their use in society is permitted unless the exposure or intake level would exceed the threshold. Genotoxicity assays are an important method to distinguish the two classes of carcinogens. However, some carcinogens have negative results in in vitro bacterial mutation assays, but yield positive results in the in vivo transgenic rodent gene mutation assay. Non-DNA damage, such as spindle poison or topoisomerase inhibition, often leads to positive results in cytogenetic genotoxicity assays such as the chromosome aberration assay or the micronucleus assay. Therefore, mechanistic considerations of tumor induction, based on the results of the genotoxicity assays, are necessary to distinguish genotoxic and non-genotoxic carcinogens. In this review, the concept of threshold of toxicological concern is introduced and the potential risk from multiple exposures to low doses of genotoxic carcinogens is also discussed.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.179-179
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• 2001

To investigate the genotoxic effect of 1, 1-dichloro-1-fluoroethane which was widely used as a cleaning solvent at the electronic part industry, the micronucleus frequencies were recorded by examining polychromatic erythrocytes in bone marrows of single i.p. injected mice at high doses and of the repeatedly inhaled rats for 13 weeks at relatively low concentrations.(omitted)

• Journal of Food Hygiene and Safety
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• v.16 no.2
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• pp.145-151
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• 2001

EpoxidiBed soy bean oil (ESBO) is a plasticizer of PVC which is being widely used as a gaskets for the lid of glass jars including baby food. Using reverse mutation assay, chromosome aberration test and micronucleus test, ESBO were evaluated the mutagenicity. In the reverse mutation test, ESBO did not induced mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, TA1537, TA102 with and without metabolic activation. In the chromosome aberration test using CHL cells, the results showed no increased structural and numerical aberrations in the concentration of sample producing cytotoxicity with and without metabolic activation. The in vivo induction of micronuclei was measured in polychromatic erythrocytes of bone marrow of young (3weeks old) and adult (6 weeks old) ddY mice of both sex. At 24 hours after treatment with ESBO 20, 10, 5, 2.5 g/B.W. kg/corn oil 10 ml by oral route animals were sacrificed and bone marrow cells were prepared for smear slides. The results showed no increased micronucleated polychromatic erythrocytes regardless of sex and age. It was concluded that water soluble ESBO did not show certain genotoxicity within our studies conducted.