• Title/Summary/Keyword: bone marrow micronucleus test

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Genotoxicily Studies of An Anticancer Agent of Camptothecin Series, CKD-602 (Camptothecin계 항암제 CKD-602의 유전독성평가)

  • 하광원;오혜영;허옥순;박장환;손수정;한의식;김종원;강일현;강혁준
    • Environmental Mutagens and Carcinogens
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    • v.18 no.2
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    • pp.129-134
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    • 1998
  • To evaluate the genotoxicity of CKD-602, an anticancer agent the in viかo reverse mutation assay using Salmonella typhimurium, the Chromosome aberration assay using Chinese hamster lung (CHL) cells and the in vivo micronucleus assay using bone marrow cells of ddY mice were performed. In the reverse mutation assay, CKD-602 did not induced mutagenicity in Salmonella typhimurium TA 98, TA 100, TA 1535, and TA 1537 strains with and without metabolic activation. In the chromosome aberration test using CHL cells, there was an increased incidence of structural aberrations induced by CKD-602 without metabolic activation during 24 and 48 hours, but CKD-602 did not induce chromosome aberration with metabolic activation. The in vivo induction of micronuclei was measured in polychromatic erythrocytes of bone marrow of male ddY mice. At 24 hours after treatment with CED-602 by i.p. once, there was an increased incidence of micronucleated polychromatic erythrocytes in bone marrow of ddY male mice.

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Genotoxicify Studies of on Antihypertensive Agent, SKP-450 (고혈압 치료제 SKP-450의 유전독성평가)

  • 하광원;오혜영;박장환;허옥순;손수정;한의식;류근호;조용백
    • Environmental Mutagens and Carcinogens
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    • v.18 no.2
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    • pp.123-128
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    • 1998
  • To evaluate the genotoxicity of SKP-450, an antihypertensive agent the in vitro reverse mutation assay using Salmonella typhimurium, the Chromosome aberration assay using Chinese hamster lung (CHL) cells and the in vivo micronucleus assay using bone marrow cells of ddY mice were performed. In the Reverse mutation test, SKP-450 did not induced mutagenicity in Salmonella typhimurium TA 98, TA 100, TA 1535 and TA 1537 with and without metabolic activation. In the chromosome aberration assay using CHL cells, there was no increased incidence of structural and numerical aberrations with and without metabolic activation. The in vivo induction of micronuclei was measured in polychromatic erythrocytes of bone marrow of male ddY mice at 30 hours after treatment with SKP-450 by p.o once. The results showed no increased incidence of micronucleated polychromatic erythrocytes in bone marrow of ddY male mice treated with SKP-450.

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Erythrocyte Micronucleus Test of Pomace Schisandra chinensis Extracts Using ICR Mouse (ICR 마우스를 이용한 오미자박 추출물의 소핵 시험)

  • Seokho, Kim;Sun Youn, Kim;Young-Suk, Kim;Jong-Min, Lim;Bon-Hwa, Ku;Kyeong Tae, Kwak;Byeong Yeob, Jeon
    • Herbal Formula Science
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    • v.30 no.4
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    • pp.259-267
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    • 2022
  • Objectives : In this study, erythrocyte micronucleus test of pomace Schisandra chinensis extracts was conducted in order to up-cycling to a high value-added industry using by-products discarded in the production process of Schisandra chinensis products and active ingredients such as dibenzocyclooctadiene lignans in Schisandra chinensis. Methods : The micronucleus test was performed according to the 'OECD Guidelines'. Including the negative control group(0 mg/kg) and the positive control group(CPA 70 mg/kg), pomace Schisandra chinensis extracts were orally administered to ICR mouse at doses of 500, 1,000, and 2,000 mg/kg. After sacrificing the experimental animals bone marrow cells were collected and micronucleated polychromatic erythrocyte were counted. And genetic toxicity was confirmed according to the frequency of micronucleus. Results : As a result of the micronucleus test, there were no changes in body weight, clinical signs, or death in any group. But, a significant increase was observed in the frequency of micronucleated polychromatic erythrocyte among polychromatic erythrocytes in the positive control group administered with CPA compared to the negative control group(p<0.05). Whereas, no significant increase was observed in the group administered with pomace Schisandra chinensis extracts compared to the negative control group. Conclusions : Pomace Schisandra chinensis extracts did not induce micronucleus in bone marrow cells of ICR mouse up to a concentration of 2,000 mg/kg, and it was judged that no genetic toxicity was observed.

Toxicological Study of SU-Eohyeol Pharmacopuncture in an In Vivo Micronucleus Test in Sprague-Dawley Rats (Sprague-Dawley 랫드를 이용한 소핵시험을 통한 SU어혈약침의 안전성 평가)

  • Ku, Jaseung;Jung, Chul;Hwang, Ji Hye
    • Korean Journal of Acupuncture
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    • v.39 no.2
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    • pp.54-62
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    • 2022
  • Objectives : The purpose of this study was to evaluate the potential of the test substance, SU-Eohyeol Pharmacopuncture (SUEP), to induce micronuclei in bone marrow cells of Sprague-Dawley (SD) Rats. Methods : The dose range preliminary study was performed first. 1 ml/animal was selected as the high dose of this study. Two additional lower dose levels (0.5 and 0.25 ml/animal) were produced by applying a geometric ratio of 2. In addition, the positive and negative control groups were set. Then, after intramuscular administration (1 ml/animal) of SUEP to 8-week-old male SD rats, an in vivo micronucleus test was performed to evaluate the induction of micronuclei in SD rat bone marrow cells. Results : As a result of the main study, the incidence of micronucleated polychromatic erythrocytes (MNPCE) in polychromatic erythrocytes (PCE) in the test substance SUEP groups was not statistically significantly different from the negative control group. In addition, the ratio of PCE to total erythrocytes in the test substance SUEP groups was not statistically significantly different from the negative control group. In the positive control group, the incidence of MNPCE in PCE was statistically significantly increased when compared to the negative control group. The ratio of PCE to total erythrocytes in the positive control group was not statistically significantly different from the negative control group. Conclusions : Based on these results, the test substance, SUEP, did not have any potential to induce micronuclei formation in bone marrow cells of rats under the conditions of this study.

The micronucleus formation in peripheral blood of mitomycin C-treated mice using supravital staining with acridine orange (마우스 말초혈액 망상적혈구를 이용한 Mitomycin C의 소핵생성효과)

  • 허문영;류재천
    • Environmental Mutagens and Carcinogens
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    • v.16 no.1
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    • pp.24-29
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    • 1996
  • In this study, the micronucleus test with peripheral blood using acridine orange coated slides was evaluated in mice treated with mitomycin C(MMC) at doses of 0.5, 1.0 and 1.5 mg/kg body weight. The peripheral bloods were obtained at 0, 24, 48 and 72h after treatment. The frequencies of micronucleated reficulocytes(MNRET) in the MMC-treated groups increased dose-dependently, and showed a peak time at 48h after treatment. We also performed the sex differences of MNRET frequency in 0.5 mg/kg MMC treated group, and we observed no sex differences in this experiment. And we evaluated the usefulness of a direct acting clastogen, N-methyl-N-nitrosourea and a indirect acting clastogen, benzo(a) pyrene as the positive control in this supravital micronucleus test. They also caused a significant increase in MNRET frequencies. These results suggest that the supravital staining micronucleus test using MNRET can be useful tool to evalulate the quantitative and qualitative assessment of genotoxicity in vivo compared to classical in vivo micronucleus test using bone-marrow cells.

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Mouse Single Oral Dose Toxicity Test and Bone Marrow Micronucleus Test of Mahwangbujaseshin-tang Extracts (마황부자세신탕(麻黃附子細辛湯)의 마우스 단회 경구투여 독성 및 골수세포를 이용한 유전독성 평가)

  • Sung, Ik-Jae;Park, Mee-Yeon;Cheon, Woo-Hyun;Kim, Jong-Dae
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.5
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    • pp.1145-1153
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    • 2009
  • The object of this study was to obtain acute information single oral dose toxicity of Mahwangbujaseshin-tang extracts, with mouse bone marrow cell micronucleus test for detecting possible genotoxicity. In order to observe the 50% lethal dose, approximate lethal dosage, maximum tolerance dosage and target organs, test articles were once orally administered to ICR mice at dose levels of 2000, 1000, 50 mg/kg according to the recommendation of KFDA Guidelines. The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after dosing according to KFDA Guidelines with organ weights of 12 types of principle organs. In addition, after twice oral treatment of Mahwangbujaseshin-tang extracts 2000, 1000 and 500 mg/kg, we checked the changes on the number of MNPCE. We could not find any mortality, clinical signs, changes in the body weight and gross findings upto 2000 mg/kg treated group. The limited dosages in rodents except for increases of lymphoid organ weights and hypertrophy encounted as results from pharmacological effects of Mahwangbujaseshin-tang extracts, immune modulator effects with some sporadic accidental findings not toxicological signs. No evidence of increases of MNPCE numbers were also detected in all three different dosages of Mahwangbujaseshin-tang extracts treated mice. The results obtained in this study suggest that the LD50 and ALD of Mahwangbujaseshin-tang extracts in mice were considered as over 2000 mg/kg because no mortalities were detected upto 2000 mg/kg that was the highest dose recommended by KFDA and OECD. And the results of mouse bone marrow micronucleus test of Mahwangbujaseshin-tang extracts is negative results.

Mouse Single Oral Dose Toxicity Test and Bone Marrow Micronucleus Test of Mahwangbujaseshin-tang Extracts (마황부자세신탕(麻黃附子細辛湯)의 마우스 단회 경구투여 독성 및 골수세포를 이용한 유전독성 평가)

  • Sung, Ik-Jae;Park, Mee-Yeon;Kim, Jong-Dae
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.24 no.1
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    • pp.124-133
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    • 2010
  • The object of this study was to obtain acute information single oral dose toxicity of Mahwangbujaseshin-tang extracts, with mouse bone marrow cell micronucleus test for detecting possible genotoxicity. In order to observe the 50% lethal dose, approximate lethal dosage, maximum tolerance dosage and target organs, test articles were once orally administered to ICR mice at dose levels of 2000, 1000, 50 mg/kg according to the recommendation of KFDA Guidelines. The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after dosing according to KFDA Guidelines with organ weights of 12 types of principle organs. In addition, after twice oral treatment of Mahwangbujaseshin-tang extracts 2000, 1000 and 500 mg/kg, we checked the changes on the number of MNPCE. We could not find any mortality, clinical signs, changes in the body weight and gross findings upto 2000 mg/kg treated group. The limited dosages in rodents except for increases of lymphoid organ weights and hypertrophy encounted as results from pharmacological effects of Mahwangbujaseshin-tang extracts, immune modulator effects with some sporadic accidental findings not toxicological signs. No evidence of increases of MNPCE numbers were also detected in all three different dosages of Mahwangbujaseshin-tang extracts treated mice. The results obtained in this study suggest that the LD50 and ALD of Mahwangbujaseshin-tang extracts in mice were considered as over 2000 mg/kg because no mortalities were detected upto 2000 mg/kg that was the highest dose recommended by KFDA and OECD. And the results of mouse bone marrow micronucleus test of Mahwangbujaseshin-tang extracts is negative results.

Genotoxic Effects of Diesel Emission Particle Extract, $HgCl_2$ and $Pb(Ac)_2$ by the Mouse Bone Marrow Micronucleus Test (마우스 골수 소핵 시험에 의한 디젤분진, $HgCl_2$$Pb(Ac)_2$의 유전독성효과)

  • 허문영;최성규;유기선;손동헌
    • Journal of Korean Society for Atmospheric Environment
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    • v.5 no.1
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    • pp.62-67
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    • 1989
  • The clastogenic effects of the diesel emission particle extract (DEPE), mercuric chloride and lead acetate were examined by the mouse bone marrow micronucleus test. DEPE had a potent clastogenic effect by intraperitoneal injection with dose-response between 100 and 300mg/kg b.w.. Mercuric chloride and lead acetate also gave a clastogenic effects but mercuric chloride only had a dose-response between 1 and 3mg/kg b.w.. When DEPE was administrated with mercuric chloride or lead acetate, the frequency of micronucleated cells was slight but not significant increase in comparision to a single treatment with DEPE alone.

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Micronucleus Test in Bone Marrow Cells and Bacterial Reverse Mutation Assay of HMC05 (HMC05의 경구투여 소핵시험 및 복귀돌연변이 시험)

  • Shin, Heung-Mook
    • The Korea Journal of Herbology
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    • v.25 no.2
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    • pp.137-144
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    • 2010
  • Objectives : We investigated genetic toxicity of HMCO5 using the Micronucleus Test in bone marrow cells of mice and Bacterial Reverse Mutation Assay in plate incorporation method according to OECD Guidelines and KFDA Guidelines. Methods : 1. Micronucleus test: The male rats were divided into 5 groups, respectively; G(1), treated with distilled water: G(2), treated with 1250mg/kg HMC05: G(3), treated with 2500mg/kg HMC05, G(4), treated with 5,000mg/kg HMC05; G(5), treated with Cyclophosphamide $H_2O$. Sterilized distilled water and HMC05 were administered for two consecutive days. Cyclophosphamide $H_2O$ was administered once on the day of 2nd administration. 2. Bacterial Reverse Mutation Aassay: Experimental groups were divided into two groups: with S-9mix(+S) or without S-9mix(-S). Each group treated with sterilized distilled water only, HMCO5(62, 185, 556, 1,667, $5,000{\mu}g$/plate) and, positive vehicles(Sodium azide, 2-Aminoanthracene, 4-Nitroquinoline N-oxide, ICR 191), respectively. Results : HMC05 did not show any changes in the number of micronucleated polychromatic erythrocytes(MNPCE) among 200 polychromatic erythrocytes compare to negative control. However, there were significant (p<0.01) increase with CPA in MNPCE. In Bacterial Reverse Mutation Aassay, no significant increases in the number of revertant colonies compared to (삭제) negative control were detected in all concentrations of HMC05. Conclusions : These results indicate that HMC05 did not show any genotoxicity against in Micronucleus test and Bacterial Reverse Mutation Aassay.

Genetic Toxicity Study of YH1715 Series, Antifungal Agents (YH1715계열 항진균제의 유전독성평가)

  • 하광원;오혜영;박장환;허옥순;손수정;한의식;이종영;김소희;강희일
    • Environmental Mutagens and Carcinogens
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    • v.18 no.2
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    • pp.93-97
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    • 1998
  • The results of chromosome aberration test in mammalian cells in culture (Chinese hamster lung fibroblast cells) showed no induction of structural and numerical aberrations by antifungal agents of YH1715 series regardless of metabolic activation. While positive control group (mitomycin C and benzo(a)pyrene) showed structural chromosome aberrations of 37% and 23%, respectively. The in vivo induction of micronuclei was measured in polychromatic erythrocytes in bone marrow of male ddY mouse given YH1715R and YH1729R at 1, 0.5, 0.25 g/kg by p.o. once. After 24 hours, animals were sacrificed and evaluated 40 the incidence of micronucleated polychromatic erythrocytes in whole erythrocytes. Although a positive response for induction of micronuclei in animals treated with mitomycin C demonstrated the sensitivity of the test system for detection of a chemical clastogen, YH1715R did not induce micronuclei in bone marrow of ddY male mice but induced cytotoxicity to bone marrow cells at the highest concentration (1 g/kg, p〈0.05), and YH1729R induced micronuclei in bone marrow of ddY male mice dose dependently (p<0.05) but did not induce cytotoxicity to bone marrow cells.

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