• 제목/요약/키워드: mammalian micronucleus test

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Mutagenicity Study of (R)-JG-381, A New Antidiabetic Agent (항당뇨물질 (R)-JG-381의 변이원성 시험)

  • 오우용;주상섭;박형근;함광수;조장섭;이선미
    • 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.

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Mutagenicity Studies of Cosmetic Dyes (2) (외용색소의 유전독성에 관한 연구(2))

  • 하광원;김명희;오혜영;허옥순;한의식
    • Journal of Food Hygiene and Safety
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    • v.13 no.2
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    • pp.135-142
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    • 1998
  • The mutagenicity of three external colorants, lake red CBA (D&C Red No.9, R-9), rhodamine B stearate (D&C Red No.37, R-37) and permanent orange (D&C Orange No.17, O-17) was evaluated. In this study, the genetic toxicity of the these dyes was examined by in vitro chromosome aberration test in cultured mammalian cells, in vivo micronucleus test in ddY mice, and somatic mutation and recombination test (SMART) in Drosophila melanogaster. Three dyes did not induce mutagenicity in chromosome aberration test and micronucleus test. But Red No.9 and Red No. 37 showed slight increase of abnormal wing spots in Drosophila melanogaster.

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Genotoxicity Assessment of Erythritol by Using Short-term Assay

  • Chung, Young-Shin;Lee, Michael
    • 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.

In vivo Micronucleus Test of Cyclohexanone and Mutagenicity Classification According to a Globally Harmonized System (Cyclohexanone의 in vivo 소핵시험을 통한 GHS 변이원성 구분)

  • Kim, Soo-Jin;Rim, Kyung-Taek;Lim, Cheol-Hong
    • Journal of Life Science
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    • v.24 no.7
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    • pp.804-811
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    • 2014
  • A micronucleus test of cyclohexanone has not yet been conducted. To classify the chemical hazard posed by cyclohexanone according to a globally harmonized system of classification and labeling of chemicals (GHS), we investigated its mutagenicity by micronucleus induction in ICR bone marrow cells of 7-weeek-old male mice. The mice were administered three dosages of the chemical for 24 hr via the oral route. After 24 hr, the mice were sacrificed, and their bone marrow cells were prepared for smearing slides. Based on counts of micronucleated polychromatic erythrocytes (MNPCEs) of 2,000 polychromatic erythrocytes, cyclohexanone did not inhibit bone marrow cell proliferation in any of the treated groups, but it resulted in micronucleus induction. According to the results of the mammalian bone marrow micronucleus test, this chemical is mutagenic and classified as category 2 in the GHS.

Genotoxicity Tests on Hyrubicin ID6105, a Novel Anthracycline Anticancer Agent (새로운 Anthracycline계 항암제 Hyrubicin ID6105에 대한 유전독성연구)

  • 장호송;정미숙;이홍섭;유정수;김태영;김윤배;강종구
    • Toxicological Research
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    • v.18 no.4
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    • pp.385-391
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    • 2002
  • The genotoxic potential of Hyrubicin lD6105, a novel anthracycline anticancer agent, was examined on bacterial mutagenicity, mammalian cell chromosome aberration and mouse micronucleus tests. In mutagenicity (Ames') test, Salmonella typhimurium strain TA98, TA100, TA1535 and TA1537, and Escherichia coli WP2uvrA- were treated with ID6105 at doses of 312.5, 625, 1,250, 2,500 and 5,000 $\mu\textrm{g}$/ plate with or without a metabolic activation system (S9 mix). Interestingly, ID6105 significantly enhanced the number of revertant colonies of TA98 strain at all dose levels used, in the presence or absence of S9 mix, without affecting other strains of S. typhimurium and E. coli. In chromosome aberration test using cultured chinese hamster lung fibroblasts, ID6105 (1.25, 2.5 and 5 $\mu\textrm{g}$/ml) did not increase the number of aberrant cells, compared with vehicle control. in the presence or absence of S9 mix. In addition, ID6105 treatment (2.5, 5 and 10 mg/kg) did not induce micronucleated polychromatic erythrocytes in mice. Taken together, it is suggested that ID6105 might not affect chromosome integrity in mammalian system in vitro and in vivo, although it may induce frame shift mutation of specific bacterial strain such os S. typhimurium TA98.

Mutagenicity and Genotoxicity Assessment of Leuconostoc lactis DMLL10 Isolated from Kimchi

  • Heejung Park;Seoyeon Lee;Sojeong Heo;Do-Won Jeong
    • Journal of Microbiology and Biotechnology
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    • v.34 no.9
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    • pp.1803-1809
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    • 2024
  • Leuconostoc lactis DMLL10 is a microorganism specific to kimchi fermentation. In this study, we sought to evaluate the toxicity of this strain, which was newly isolated from kimchi, to determine its safety as a food ingredient. Bacterial reverse mutation assay, chromosomal aberration assay, and mammalian cell in vitro micronucleus assay were performed to assess the genetic toxicity of Leu. lactis DMLL10. The strain did not induce mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, TA1537, or Escherichia coli WP2uvrA, with or without metabolic activation of S9 mixture. The oral administration of Leu. lactis DMLL10 also did not significantly increase the number of micronucleated polychromatic erythrocytes, or the mean ratio of polychromatic to total erythrocytes. Additionally, Leu. lactis DMLL10 did not cause a significant chromosomal aberration in CHU/IL cells in the presence or absence of S9 activation. Therefore, Leu. lactis DMLL10 can be suggested as a functional food ingredient with reliability and safety.

The First Report to Evaluate Safety of Cyanobacterium Leptolyngbya sp. KIOST-1 for Use as a Food Ingredient: Oral Acute Toxicity and Genotoxicity Study

  • Lee, Youngdeuk;Kim, Taeho;Lee, Won-Kyu;Ryu, Yong-Kyun;Kim, Ji Hyung;Jeong, Younsik;Park, Areumi;Lee, Yeon-Ji;Oh, Chulhong;Kang, Do-Hyung
    • Journal of Microbiology and Biotechnology
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    • v.31 no.2
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    • pp.290-297
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    • 2021
  • Leptolyngbya sp. KIOST-1 (LK1) is a newly isolated cyanobacterium that shows no obvious cytotoxicity and contains high protein content for both human and animal diets. However, only limited information is available on its toxic effects. The purpose of this study was to validate the safety of LK1 powder. Following Organisation for Economic Co-operation and Development (OECD) guidelines, a single-dose oral toxicity test in Sprague Dawley rats was performed. Genotoxicity was assessed using a bacterial reverse mutation test with Salmonella typhimurium (strains TA98, TA100, TA1535, and TA1537) and Escherichia coli WP2 uvrA, an in vitro mammalian chromosome aberration test using Chinese hamster lung cells, and an in vivo mammalian erythrocyte micronucleus test using Hsd:ICR (CD-1) SPF mouse bone marrow. After LK1 administration (2,500 mg/kg), there were no LK1-related body weight changes or necropsy findings. The reverse mutation test showed no increased reverse mutation upon exposure to 5,000 ㎍/plate of the LK1 powder, the maximum tested amount. The chromosome aberration test and micronucleus assay demonstrated no chromosomal abnormalities and genotoxicity, respectively, in the presence of the LK1 powder. The absence of physiological findings and genetic abnormalities suggests that LK1 powder is appropriate as a candidate biomass to be used as a safe food ingredient.

The Genotoxicity Study of Molinate, an Herbicide, in Bacterial Reversion, in vitro and in vivo Mammalian System

  • Kim, Youn-Jung;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.2 no.3
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    • pp.176-184
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    • 2006
  • The controversy on genotoxicity of molinate, an herbicide, has been reported in bacterial system, and in vitro and in vivo mammalian systems. To clarify the genotoxicity of molinate, we performed bacterial gene mutation test, in vitro chromosome aberration and mouse lymphoma $tk^{+/-}$ gene assay, and in vivo micronucleus assay using bone marrow cells and peripheral reticulocytes of mice. In bacterial gene mutation assay, no mutagenicity of molinate ($12-185{\mu}g/plate$) was observed in Salmonella typhimurium TA 98, 100, 1535 and 1537 both in the absence and in the presence of S-9 metabolic activation system. The clastogenicity of molinate was observed in the presence ($102.1-408.2\;{\mu}g/mL$) of metabolic activation system in mammalian cell system using Chinese hamster lung fibroblast. However, no clastogenicity was observed in the absence ($13.6-54.3\;{\mu}g/mL$) of metabolic activation system. It is suggested that the genotoxicity of molinate was derived some metabolites by metabolic activation. Molinate was also subjected to mouse lymphoma L5178Y $tk^{+/-}$ cells using microtiter cloning technique. In the absence of S-9 mixture, mutation frequencies (MFs) were revealed $1.4-1.9{\times}10^{-4}$ with no statistical significance. However, MFs in the presence of metabolic activation system revealed $3.2-3.4{\times}10^{-4}$ with statistical significance (p<0.05). In vivo micronucleus (MN) assay using mouse bone marrow cells, molinate revealed genotoxic potential in the dose ranges of 100-398 mg/kg of molinate when administered orally. Molinate also subjected to acridine orange MN assay with mouse peripheral reticulocytes. The frequency of micronucleated reticulocytes (MNRETs) induced 48 hr after i.p. injection at a single dose of 91, 182 and 363 mg/kg of molinate was dose-dependently increased as $10.2{\pm}4.7,\;14.6{\pm}3.9\;and\;28.6{\pm}6.3\;(mean{\pm}SD\;of\;MNRETs/2,000\;reticulocytes)$ with statistical significance (p<0.05), respectively. Consequently, genotoxic potential of molinate was observed in in vitro mammalian mutagenicity systems only in the presence of metabolic activation system and in vivo MN assay using both bone marrow cells and peripheral reticulocytes in the dose ranges used in this experiment. These results suggest that metabolic activation plays a critical role to express the genotoxicity of molinate in in vitro and in vivo mammalian system.

Mutagenicity Study of Recombinant Human Erythropoietin(rhEPO) (천연형 인 적혈구 조혈인자의 변이원성시험)

  • Kang, Kyung-Koo;Cho, Hyeon;Kim, Dong-Hwan;Baik, Nam-Gi;Kim, Won-Bae
    • Biomolecules & Therapeutics
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    • v.6 no.1
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    • pp.56-62
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    • 1998
  • Mutagenicity of recombinant human erythropoietin (rhEPO) was examined in the reverse mutation test on bacteria, in the chromosomal aberration test on cultured mammalian cells and in the micronucleus test on mice. The reverse mutation test was performed by a plate incorporation method with or wothout a metabolic activation system (59 Mix) using Salmonella typhimurium strain TA100, TA1535, TA98 and TA 1537. The rhEPO did not significantly increase revertant colonies in any of the test strains under any conditions at dose levels ranging from 1000 H/ml to 62.5 lu/plate, compared with the vehicle control. In the chromosomal aberration test using cultured Chinese Hamster Lung (CHL) cells, the number of aberrant cells was not increased in the presence or absence of 59 Mix at concentrations of 1000 lU/ml to 250 lU/ml, compared with the vehicle control. In the micronucleus test, male ICR mice were given rhEPO intraperitoneally at a dose level of 25000, 12500 and 6250 lU/kg. The incidence of bone marrow micronucleated polychromatic erythrocytes was not different from that of the vehicle control. From these results, rhEPO is considered to be non-mutagenic under the present test conditions.

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Mutagenicity of DA-5018, a Non-narcotic Analgesic Agent (비 마약성 진통제 DA-5018의 변이원성 연구)

  • 강경구;백남기;김원배;양중익
    • Biomolecules & Therapeutics
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    • v.4 no.3
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    • pp.224-231
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    • 1996
  • DA-5018, a non-narcotic analgesic agent, was examined for mutagenicity in the reverse mutation test on bacteria, chromosomal aberration test on cultured mammalian cells and micronucleus test on mice. The reverse mutation test was performed by a plate incorporation method with or without a metabolic activation system(S9 mix) using Salmonella typhimurium strain TA100, TA1535, TA98 and TA1537. DA-5018 did not significantly increase revertant colonies in any of the test strains under any conditions at concentrations ranging from 0.0049 to 1.25 mg/plate, compared with the vehicle control. In the chromosomal aberration test using cultured Chinese Hamster Lung(CHL) cells, DA-5018 did not increase the number of aberrant cells in the presence or absence of S9 mix at concentrations of 0.016 mM/plate to 0.25 mM/plate, compared with the vehicle control. In the micronucleus test, male ICR mice were given DA-5018 intraperitoneally at a dose level of 0.55, 1.10 and 2.20 mg/kg. The incidence of bone marrow micronucleated polychromatic erythrocytes in the DA-5018 treated mice was not significantly different from that of the vehicle control. These results indicate that DA-5018 does not have mutagenic potential under the present test conditions.

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