• Title/Summary/Keyword: bone marrow micronucleus test

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Suppressive Effect of N-Acetylcysteine on the Adriamycin-Induced Micronuclei Formation in Mouse Bone-marrow Cells (생쥐 골수세포에서 아드리아마이신의 소핵생성에 미치는 N-마세틸시스테인의 억제효과)

  • 손수정;허인회;최성규;허문영
    • YAKHAK HOEJI
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    • v.37 no.3
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    • pp.278-285
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    • 1993
  • The anticlastogenic effect of N-acetylcysteine was tested in vivo in mouse bone-marrow micronucleus assay. The frequencies of micronuclei induced by adriamycin (5 mg/kg i.p.) in bonemarrow cells were decreased by the oral administration of N-acetylcysteine at 12 h before adriamycin injection. The observed suppressing effect was not a reflection of a delay in the formation of micronuclei by the cytotoxic effect of N-acetylcysteine. The anticlastogenic effects of SH compound including N-acetylcysteine, cysteine, cystine, S-carboxy methylcysteine and glutathione were also investigated by the multiple pretreatment. Each SH compound was administered orally every day for 5 days and adriamycin (5 mg/kg i.p.) was injected at 24h after the last dose of test compound. N-acetylcysteine and glutathione showed significantly the suppressive effect at dose of 10 and 25 mg/kg for N-acetylcysteine and at the dose of 25 mg/kg for glutathione. Our study suggests that N-acetylcysteine is capable of protecting the chromosomal damages in the normal cells during cancer chemotherapy by adriamycin, and may act as an anticlastogen against induction of micronuclei by superoxide generating agent such as adriamycin.

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Micronucleus Test of PolycanTM, β-Glucan Originated from Aureobasidium, in Bone Marrow Cells of Male ICR Mice

  • Lee, Hyeung-Sik;Cho, Hyung-Rae;Yang, Kun-Ju;Moon, Seung-Bae;Park, Bok-Ryeon;Shin, Hyun-Dong;Jang, Hee-Jeong;Kim, Lin-Su;Ku, Sae-Kwang
    • Toxicological Research
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    • v.24 no.1
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    • pp.11-15
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    • 2008
  • In this research the genotoxic effect of $Polycan^{TM}$ ${\beta}$-glucans originated from Aureobasidium pullulans SM-2001, was evaluated using the mouse micronucleus test. $Polycan^{TM}$ was administered once a day for 2 days by oral gavage to male ICR mice at doses of 1000, 500 and 250 mg/kg. Cyclophosphamide was used as a known genotoxic agent in a positive control group. The appearance of a micronucleus is used as an index for genotoxic potential. The results obtained indicated that $Polycan^{TM}$ shows no genotoxicity effect up to 1000 mg/kg dosing levels. In addition, it is also considered that there were no problems from cytotoxicity of $Polycan^{TM}$ tested in this study because the polychromatic erythrocyte ratio was detected as > 0.47 in all tested groups.

Micronucleus Test of DHU001, a Polyherbal Formula, in Bone Marrow Cells of Male ICR Mice

  • Roh, Seong-Soo;Lee, Hyeung-Sik;Ku, Sae-Kwang
    • Toxicological Research
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    • v.25 no.4
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    • pp.225-230
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    • 2009
  • The genotoxic effects of DHU001, a polyherbal formula were evaluated using the mouse micronucleus test. DHU001 was administered once a day for 2 continuous days by oral gavage to male ICR mice at doses of 2000, 1000 and 500 mg/kg. Cyclophosphamide was used as a known genotoxic agent in a positive control. The appearance of a micronucleus is used as an index for genotoxic potential. In addition, the changes on the total white blood cells and differential counts on the lymphocytes, neutrophils, eosinophils, basophils and monocytes in the prepared blood smears were also conducted to observe the possible immunosuppression. The results indicats that DHU001 showed no genotoxicity effects up to 2000 mg/kg dosing levels and did not influenced on the total white blood cells and differential counts. In addition, it is also considered that there were no problems from cytotoxicity of DHU001 tested in this study because the polychromatic erythrocyte ratio was detected as > 0.41 in all tested groups.

Micronucleus Test of Kong-Jin-Dan, a Polyherbal Formula, in Bone Marrow Cells of Male ICR Mice

  • Lee, Sang-Nam;Park, Ji-Ha;Ku, Sae-Kwang
    • Toxicological Research
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    • v.24 no.3
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    • pp.213-218
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    • 2008
  • In this research, the genotoxic effects of Kong-Jin-Dan(KJD), a polyherbal formula were evaluated using the mouse micronucleus test. KJD was administered once a day for 2 continuous days by oral gavage to male ICR mice at doses of 2000, 1000 and 500 mg/kg. Cyclophosphamide was used as a known genotoxic agent in a positive control. The appearance of a micronucleus is used as an index for genotoxic potential. In addition, the changes on the total white blood cells and differential counts on the lymphocytes, neutrophils, eosinophils, basophils and monocytes in the prepared blood smears were also conducted to observe the possible immunosuppress. The results obtained indicated that KJD shows no genotoxicity effects up to 2000 mg/kg dosing levels, but KJD shows slight increased trends in the blood total leukocyte numbers as pharmacological effects of immune stimulation. In addition, it is also considered that there were no problems from cytotoxicity of KJD tested in this study because the polychromatic erythrocyte ratio was detected as > 0.42 in all tested groups.

Evaluation of in vivo Genotoxicity of Plant Flavonoids, Quercetin and Isoquercetin (식물유래 플라보노이드 Quercetin과 Isoquercetin의 생체 내 유전독성평가)

  • Pak, Bumsoo;Han, Sehee;Lee, Jiyeon;Chung, Young-Shin
    • Journal of Food Hygiene and Safety
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    • v.31 no.5
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    • pp.356-364
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    • 2016
  • In vivo genotoxic potential of isoquercetin, a plant common flavonoid, in comparison with quercetin was investigated for the DNA breakage and the clastogenicity endpoints. Male ICR mice were administered by oral gavage for 3 days with $3{\times}0.5%$ carboxymethyl cellulose (CMC), 3 ${\times}$ isoquercetin (250, 500 mg/kg/day), 3 ${\times}$ quercetin (250, 500 mg/kg/day) and 2 ${\times}$ ethyl methanesulfonate (EMS, 200 mg/kg/day). Tissues were collected 48 hours after the first treatment and within 3 hours after the last treatment. The DNA damages were evaluated using Comet assay in liver and stomach, while the clastogenicities were determined using micronucleus test in bone marrow of same animals. The treatment of isoquercetin as well as quercetin did not cause the DNA damages in liver and stomach, and not induce the frequencies of micronucleus polychromatic erythrocytes in bone marrow. In conclusion, isoquercetin as well as quercetin did not cause the DNA breakages and the chromosomal damages in vivo system in these study conditions.

Radioprotective Effect of Panax Ginseng in Mouse Bone-marrow (생쥐에서 방사선방호제로서의 인삼효과에 관한 연구)

  • Chae, Ki-Moon;Choi, Keun-Hee;Kim, Young-Ho;Kim, Kwang-Yoon;Bom, Hee-Seung;Kim, Ji-Yeul;Lee, Chong-Bin
    • Journal of Radiation Protection and Research
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    • v.22 no.1
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    • pp.1-7
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    • 1997
  • Radiation protection by post-irradiation injection of the ginseng extract in mice was studied. Male ICR mice, 7 weeks old, were orally injected with ginseng extrat(100mg/kg) for 10 days, and with physiologocal saline as the control. Immediately after final injection, mice were whole body irradiated with 5.08Gy(Cs-137 ${\gamma}$-ray, central dose rate : 654Gy/h) which induced Bone marrow death. At 24h after irradiation, micronucleus test and metaphase analysis in bone-marrow were carried, blood cell were counted and the survival rate were carried for 30 days after the irradiation. Stimulated recovery by the extract was observed in thrombocyte count, but that phenomenom was not showed in the erythrocyte and leucocyte counts. The 30-day survival ratio was 5% and 65% for the control and experimental group. Frequencies of micronuclei per 1000 polychromatic erythrocytes were 79.5${\pm}$1.5 in experimental group, 185.9${\pm}$35.8 in control. And Abnormal chromosomes per 50 metaphases were 112 in experimental group and 143 in control.

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Assurance on the Genotoxicological Safety of Fermented Vegetables Pasteurized by Gamma Irradiation

  • Yook, Hong-Sun;Byun, Myung-Woo;Song, Hyun-Pa;Lee, Ju-Woon;Kim, Kwan-Soo;Kim, Kwang-Hoon;Lee, Ho-Joon;Kim, Dong-Ho
    • Food Science and Biotechnology
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    • v.14 no.1
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    • pp.137-142
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    • 2005
  • The genotoxicological safety of fermented vegetables pasteurized by gamma irradiation was examined to consider the possibility of the application of irradiation for extending of fermented vegetables. A fermented vegetable was irradiated at 20 kGy to assure its toxicological safety even at a high dose of radiation. The Ames test with Salmonella typhimurium (TA98, TA100, TA1535, TA1537) and Escherchia coli (WP2), and the chromosomal aberration test in Chinese hamster lung (CHL) cells were performed. In vivo micronucleus test were conducted in mouse bone marrow cells. With or without metabolic activation, negative results were obtained in the Ames test and the chromosomal aberration test. In the micronucleus test, there was no enhancement in the formation of micronucleus, and there were no such significant differences between the irradiated and non-irradiated samples. The observed results indicated that, a level of 20 kGy of gamma irradiation on the fermented vegetable did not bring about any genotoxic effects under the described experimental conditions.

General and Genetic Toxicology of Enzyme-Treated Ginseng Extract - Toxicology of Ginseng Rh2+ -

  • Jeong, Mi-Kyung;Cho, Chong-Kwan;Yoo, Hwa-Seung
    • Journal of Pharmacopuncture
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    • v.19 no.3
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    • pp.213-224
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    • 2016
  • Objectives: Ginseng Rh2+ is enzyme-treated ginseng extract containing high amounts of converted ginsenosides, such as compound k, Rh2, Rg3, which have potent anticancer activity. We conducted general and genetic toxicity tests to evaluate the safety of ginseng Rh2+. Methods: An acute oral toxicity test was performed at a high-level dose of 4,000 mg/kg/day in Sprague-Dawley (SD) rats. A 14-day range-finding study was also conducted to set dose levels for the 90-day study. A subchronic 90-day toxicity study was performed at dose levels of 1,000 and 2,000 mg/kg/day to investigate the no-observed-adverse-effect level (NOAEL) of ginseng Rh2+ and target organs. To identify the mutagenic potential of ginseng Rh2+, we conducted a bacterial reverse mutation test (Ames test) using amino-acid-requiring strains of Salmonella typhimurium and Escherichia coli (E. coli), a chromosome aberration test with Chinese hamster lung (CHL) cells, and an in vivo micronucleus test using ICR mice bone marrow as recommended by the Korean Ministry of Food and Drug Safety. Results: According to the results of the acute oral toxicity study, the approximate lethal dose (ALD) of ginseng Rh2+ was estimated to be higher than 4,000 mg/kg. For the 90-day study, no toxicological effect of ginseng Rh2+ was observed in body-weight changes, food consumption, clinical signs, organ weights, histopathology, ophthalmology, and clinical pathology. The NOAEL of ginseng Rh2+ was established to be 2,000 mg/kg/day, and no target organ was found in this test. In addition, no evidence of mutagenicity was found either on the in vitro genotoxicity tests, including the Ames test and the chromosome aberration test, or on the in vivo in mice bone marrow micronucleus test. Conclusion: On the basis of our findings, ginseng Rh2+ is a non-toxic material with no genotoxicity. We expect that ginseng Rh2+ may be used as a novel adjuvant anticancer agent that is safe for long-term administration.

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.

Cytogenetic Radiation Adaptive Response Assessed by Metaphase Analysis and Micronuclei Test in Human Lymphocytes and Mouse Bone Marrow Cells (인체말초혈액 림프구와 마우스골수세포에서 중기염색체 분석법과 미소핵검사법을 이용한 방사선적응반응 평가)

  • Min, Jung-Jun;Bom, Hee-Seung;Lee, Seung-Yeon;Choi, Keun-Hee;Jeong, Hwan-Jeong;Song, Ho-Cheon;Kim, Ji-Yeul
    • The Korean Journal of Nuclear Medicine
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    • v.32 no.6
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    • pp.525-533
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    • 1998
  • Purpose: Radiation adaptive response in human peripheral lymphocytes and mouse bone marrow cells was investigated using both metaphase analysis and micronucleus assay. We assessed the correlation between both tests. Materials and Methods: Two groups of the human peripheral lymphocytes and mouse bone marrow cells were exposed to low dose (conditioning dose, 0,18 Gy) or high dose (challenging dose, 2 Gy) ${\gamma}$-rays. The other 4 groups were exposed to low dose followed by high dose after several time intervals (4, 7, 12, and 24 hours, respectively). The frequencies of chromosomal aberrations in metaphase analysis and micronuclei in micronucleus assay were counted. Results: Chromosomal aberrations and micronuclei of preexposed group were lower than those of the group only exposed to high dose radiation. Maximal reduction in frequencies of chromosomal aberrations were observed in the group to which challenging dose was given at 7 hour after a conditioning dose (p<0.001). Metaphase analysis and micronucleus assay revealed very good correlation in both human lymphocytes and mouse bone marrow cells (r=0.98, p<0.001 ; r=0.99, p=0.001, respectively). Conclusion: Radiation adaptive response could be induced by low dose irradiation in both human lymphocytes and mouse bone marrow cells. There was a significant correlation between metaphase analysis and micronucleus assay.

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