• Title/Summary/Keyword: Chromosomal aberration assay

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Study on Mutagenicity of DehydroevodiamineㆍHCl(DHED) (치료제 DehydroevodiamineㆍHCl(DHED)의 변이원성 연구)

  • 성이숙;정성윤;정주연;채규영;진미령;최봉웅;장병모;김대경
    • YAKHAK HOEJI
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    • v.46 no.3
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    • pp.208-212
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    • 2002
  • Dehydroevodiamine HCl (DHED), which is a component separated from Evodia rutaecarpa Bentham, has novel anticholinesterase and antiamnesic activities in the scopolamine-induced amnesia model. Several studies suggest that DHED might be an effective drug for the Alzheimer's disease and the vascular type of dementia. In order to evaluate the mutagenic potential of DHED, Salmonella typhimurium reversion assay, chromosomal aberration test on Chinese hamster lung cells, in vivo micronucleus assay using mouse bone marrow cells, and comet assay were performed. DHED did not increase the number of revertant in the reverse mutation test using Salmonella typhimurium TA1535, TA1537, TA98, TA100. DHED HCl, at concentration of 5 and 10 $\mu\textrm{g}$/mι, increased the number of chromosome aberrated Chinese hamster lung cells with 5 and 10%, respectively. In mouse micronucleus test, no significant increase in the occurrence of micronucleated polychromatic erythrocyte was observed in ICR mice orally administered with DHED. DHED was tested for ability to induce genotoxic effect in L5178Y cells (mouse lymphoma cells) using the single cell gel electrophoresis assay (comet assay). In comet assay, tail moment did not increase in L5178Y cells treated with 10, 100, 300 $\mu$M DHED.

Evaluation of Genotoxicity of Water and Ethanol Extracts from Rhus verniciflua Stokes(RVS)

  • Kim, Ji-Young;Oh, Se-Wook;Han, Dae-Seok;Lee, Michael
    • 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.

Genotoxicological Safety of High-Dose Irradiated Porridges (고선량 조사된 시판 분말죽의 유전독성학적 안전성평가)

  • Kang, Il-Jun;Kang, Young-Hee;Chung, Cha-Kwon;Oh, Sung-Hoon;Lee, Ju-Woon;Byun, Myung-Woo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.34 no.2
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    • pp.261-266
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    • 2005
  • Gamma irradiation at 30 kGy was applied to porridge to evaluate its possible genotoxicity. The genotoxicity of irradiated porridge was evaluated by Salmonella Typhimurium reversion assay, chromosomal aberration test and in vivo micronucleus assay. The results were negative in the bacterial reversion assay with S. Typhimurium TA98, TA100, TA1535 and TA1537. No mutagenicity was detected in the assay both with and without metabolic activation. In chromosomal aberration tests with CHL cells and in vivo mouse micronucleus assay, no significant difference in the incidences of chromosomal aberration and micronuclei was observed between nonirradiated and 30 kGy-irradiated porridge. These results indicate that porridge irradiated at 30 kGy did not show any genotoxic effects under these experimental conditions.

Evaluation of the genetic toxicity of synthetic chemicals (V) -in vitro Chromosomal Aberration Assay with 17 chemicals in Chinese Hamster Lung Cells-

  • Ryu, Jae-Chun;Kim, Kyung-Ran;Kim, Youn-Jung;Choi, Hae-Yeon
    • 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.

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Evaluation of the Genetic Toxicity of Cyclopentane and Ammonium Nitrate - In vitro Mammalian Chromosomal Aberration Assay in Chinese Hamster Ovary Cells

  • Kim, Soo-Jin;Rim, Kyung-Taek;Kim, Jong-Kyu;Kim, Hyeon-Yeong;Yang, Jeong-Sun
    • Safety and Health at Work
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    • v.2 no.1
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    • pp.17-25
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    • 2011
  • Objectives: In this study, the in vitro mammalian chromosomal aberration (CA) assay was conducted to gain additional information concerning the hazards associated with the use of cyclopentane and ammonium nitrate. While these two chemicals had already been tested by many methods, they had not been studied in the CA test. Methods: The assay was performed using the ovarian infantile cell (CHO-K1 cell), by the direct method (-S9) and by the metabolic activated method (+S9 mix). Results: Using the direct method, the 7 dosages in a 48 hour treatment group did not show that the frequency of CA is proportion to the dosage addition. The frequency of CA is not proportion to the dosage addition for a 6 hour treatment using the metabolic activated method. Conclusion: From these findings, it was decided that the 2 chemicals do not induce chromosomal aberrations under the tested conditions.

Evaluation of the Genetic Toxicity of Synthetic Chemicals (XIII) - Single Cell Gel Electrophoresis of Benzoyl Chloride, 2-Propyn-1-ol, and 2-Phenoxyethanol in Chinese Hamster lung Fibroblast -

  • Ryu, Jae-Chun;Kim, Youn-Jung
    • Environmental Mutagens and Carcinogens
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    • v.24 no.2
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    • pp.79-84
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    • 2004
  • Three synthetic chemicals, benzoyl chloride, 2-propyn-l-ol, and 2-phenoxy ethanol were selected for genotoxicity testing, based on production quantity and available genotoxic data. In our previous report, benzoyl chloride induced chromosomal aberrations in Chinese hamster lung (CHL) fibroblast in vitro with and without metabolic activation, while 2-propyn-l-ol and 2-phenoxy ethanol induced only with metabolic activation. To compare the genotoxicity of chromosome aberration assay, the single cell gel electrophoresis (comet) assay subjected using CHL cells. As a result, statistically significant differences of tail moment values of benzoyl chloride, 2-propyn-1-ol, and 2-phenoxy ethanol were observed compared with control values on almost all concentrations with S9 or without S9 metabolic activation system. This results suggest that genotoxic results of the comet assay and the chromosome aberration assay show correlationship of genotoxicity in the CHL fibroblast. In summary, the positive result of chromosome aberration of benzoyl chloride, 2-propyn-l-ol, and 2-phenoxy ethanol was also induced DNA damages in comet assay with same cell line. Consequently, comet assay will be useful and more accurate tool to detect and to confirm the genotoxicity especially DNA damages in CHL fibroblast.

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Acute and Genetic Toxicity Study of DK1002, a Drug Candidate for Analgesics (DK1002에 대한 급성독성시험 및 유전독성에 관한 연구)

  • Ryu, Jae-Chun;Kim, Kyung-Ran;Kim, Hyun-Joo;Jung, Sang-Oun;Kim, Myung-Kuk;Park, Hee-Sock;Kim, Yong-Hae
    • Toxicological Research
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    • v.14 no.3
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    • pp.427-433
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    • 1998
  • The acute and genetic toxicity of DK1002 was subjected in this study. DK1002 which is a morphine-like new drug candidate synthesized by Dong-Kook Pharmaceutical Co. Ltd. is now under developing as a analgesics that have better drug efficacy and least addictive property. In acute toxicity study, the 50% lethal doses ($LD_{50}$) of DK1002 were determined as>2000mg/kg (p.o.), 237.0mg/kg(i.p.), 57.5mg/kg(i.v.), and 1266.9mg/kg (s.c.). And also, to study the genotoxicity of DK1002, we performed bacterial reversion assay with Salmonella typhimurium TA98, TA100, TA1535, and TA1537, and in vitro chromosomal aberration assay with Chinese hamster lung cells in the presence and absence of S-9 metabolic activation system. In vivo micronucleus assay using mouse bone marrow cells was also performed. From these results, DK1002 was revealed nonmutagenic potential in S. typhimurium TA98, TA100, TA1535, and TA537 both in the absence and presecne of metablic activation system. No clastogenicity of DK1002 was observed in chromosomal aberration assay in vitro as well as in micronucleus assay in vivo.

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In Vitro Genotoxicity Assessment of a Novel Resveratrol Analogue, HS-1793

  • Jeong, Min Ho;Yang, Kwangmo;Lee, Chang Geun;Jeong, Dong Hyeok;Park, You Soo;Choi, Yoo Jin;Kim, Joong Sun;Oh, Su Jung;Jeong, Soo Kyung;Jo, Wol Soon
    • Toxicological Research
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    • v.30 no.3
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    • pp.211-220
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    • 2014
  • Resveratrol has received considerable attention as a polyphenol with various biological effects such as anti-inflammatory, anti-oxidant, anti-mutagenic, anti-carcinogenic, and cardioprotective properties. As part of the overall safety assessment of HS-1793, a novel resveratrol analogue free from the restriction of metabolic instability and the high dose requirement of resveratrol, we assessed genotoxicity in three in vitro assays: a bacterial mutation assay, a comet assay, and a chromosomal aberration assay. In the bacterial reverse mutation assay, HS-1793 did not increase revertant colony numbers in S. typhimurium strains (TA98, TA100, TA1535 and TA1537) or an E. coli strain (WP2 uvrA) regardless of metabolic activation. HS-1793 showed no evidence of genotoxic activity such as DNA damage on L5178Y $Tk^{+/-}$ mouse lymphoma cells with or without the S9 mix in the in vitro comet assay. No statistically significant differences in the incidence of chromosomal aberrations following HS-1793 treatment was observed on Chinese hamster lung cells exposed with or without the S9 mix. These results provide additional evidence that HS-1793 is non-genotoxic at the dose tested in three standard tests and further supports the generally recognized as safe determination of HS-1793 during early drug development.

Protection against Whole Body γ-Irradiation Induced Oxidative Stress and Clastogenic Damage in Mice by Ginger Essential Oil

  • Jeena, Kottarapat;Liju, Vijayasteltar B;Ramanath, Viswanathan;Kuttan, Ramadasan
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.1325-1332
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    • 2016
  • Radioprotective effects of ginger essential oil (GEO) on mortality, body weight alteration, hematological parameters, antioxidant status and chromosomal damage were studied in irradiated mice. Regression analysis of survival data in mice exposed to radiation yielded LD50/30 as 7.12 and 10.14 Gy for control (irradiation alone) and experimental (GEO-treated irradiated) mice, respectively, with a dose reduction factor (DRF) of 1.42. In mice exposed to whole-body gamma-irradiation (6 Gy), GEO pre-treatment at 100 and 500 mg/kg b.wt (orally) significantly ameliorated decreased hematological and immunological parameters. Radiation induced reduction in intestinal tissue antioxidant enzyme levels such as superoxide dismutase, catalase, glutathione peroxidase and glutathione was also reversed following administration of GEO. Tissue architecture of small intestine which was damaged following irradiation was improved upon administration of GEO. Anticlastogenic effects of GEO were studied by micronuclei assay, chromosomal aberration and alkaline gel electrophoresis assay. GEO significantly decreased the formation of micronuclei, increased the P/N ratio, inhibited the formation of chromosomal aberrations and protected agaisnt cellular DNA damage in bone marrow cells as revealed by comet assay. These results are supportive of use of GEO as a potential radioprotective compound.

Genotoxicological Safety Evaluation of Crude Antifungal Compounds Produced by Bacillus subtilis SN7 (Bacillus subtilis SN7이 생성한 조항균 물질의 유전독성학적 안정성평가)

  • Chang, Hae-Choon;Koh, Sang-Bum;Lee, Jae-Joon
    • The Korean Journal of Community Living Science
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    • v.28 no.1
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    • pp.131-141
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    • 2017
  • This study was carried out to perform genotoxicological safety evaluation of crude antifungal compounds produced by Bacillus subtilis SN7 (B. subtilis SN7) isolated from meju. Bacterial reverse mutation assay with Salmonella typhimurium TA98, TA100, TA1535, and TA1537 or Escherichia coli WP2uvrA in the presence and absence of the S9 metabolic activation system was carried out, and the crude antifungal compounds produced by B. subtilis SN7 showed no significant increase in the number of revertant colonies. In the chromosomal aberration tests using Chinese hamster lung (CHL) cells, sample treatment groups showed no increase in the frequency of chromosome aberrations compared to the negative control group. Furthermore, in the micronucleus formation test, the crude antifungal compounds showed no significance increase in the frequency of polychromatic erythrocytes with micronuclei. These results suggest that the crude antifungal compounds produced by B. subtilis SN7 isolated from meju showed no harmful genotoxic effects.