• Title/Summary/Keyword: In vitro genotoxicity

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Genotoxicity and Interference with Cell Cycle Activities by an Ethanolic Extract from Thai Plumbago indica Roots in Human Lymphocytes in vitro

  • Thitiorul, Sumon;Ratanavalachai, Treetip;Tanuchit, Sermkiat;Itharat, Arunporn;Sakpakdeejaroen, Intouch
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2487-2490
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    • 2013
  • In Thai traditional medicine, Plumbago indica or Jetamul-Pleung-Dang in Thai is known to have health benefit especially for anti-inflammatory, antibacterial, and antitumor activities. However, the mechanisms of its action are still uncertain. One of which might be genotoxic effects. In the present study, we investigated the genotoxicity of an ethanolic extract of Plumbago indica root (EEPIR) by sister chromatid exchange (SCE) assay in human lymphocytes. Results have shown that all treatments with EEPIR ($12.5-100{\mu}g/ml$) could induce cell cycle delay as shown by significant increase in the number of metaphase cells in the first cell cycle but neither in the second nor the third cell cycle. Only at concentrations of 25, 50, and $100{\mu}g/ml$ were SCE levels significantly increased above that of the control (p<0.05). EEPIR at a concentration of $500{\mu}g/ml$ induced cell death as few mitotic cells were shown. Accordingly, EEPIR ($25-100{\mu}g/ml$) is genotoxic in human lymphocytes and cytotoxic at concentrations of ${\geq}500{\mu}g/ml$ in vitro. Therefore, these activities of the EEPIR could serve its potential therapeutic effects, especially as an anticancer agent. Further study of EEPIR in vivo is now needed to support this in vitro evidence.

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.

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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Study on Genotoxicity of Crocin, a Component of Gardenia Fruit, in Bacterial and Mammalian Cell Systems

  • Choi, Hae-Yeon;Kim, Youn-Jung;Jeon, Hee-Kyung;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.4 no.4
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    • pp.285-292
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    • 2008
  • Crocin is one of the major components of gardenia fruit and saffron which are widely used as natural food colorants and as traditional Chinese medicines. However, the genotoxicity data on crocin are not sufficient for safety evaluation. The purpose of this study was the examination of the genotoxicity on crocin from gardenia yellow in bacterial and mammalian cells, using various genotoxic battery testing assays and the influence of crocin on methyl methanesulfonate (MMS) and ${H_2}{O_2}$-induced DNA damage in vitro, using single cell gel electrophoresis (comet) assay. From results, no considerable mutagenicity and clastogenicity were seen in bacteria and mammalian cells treated with crocin, by Ames test, chromosomal aberration assay, ${tk}^{+/-}$ gene forward mutation assay and comet assay. And, post-treatment with crocin significantly suppressed ${H_2}{O_2}$-induced DNA damage in a dose-dependent manner. In conclusion, the findings of the present study and other previous observations indicate that crocin has no genotoxic potential. And it showed that crocin clearly repressed the genotoxic potency of ${H_2}{O_2}$. These results suggest that anti-oxidative effects of crocin may be involved in the protective effects of DNA damage.

Evaluation of the Genetic Toxicity of Synthetic Chemical (XVII) -In vitro Mouse Lymphoma Assay and In vitro Supravital Micronucleus Assay with 1, 2-Dichlorobenzene

  • Kim, Youn-Jung;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.3 no.2
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    • pp.113-118
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    • 2007
  • Chlorobenzenes due to their acute toxicity and the capability of bioaccumulating are of great health and environmental concern. Especially, 1, 2-dichlorobenzene (CAS No. 95-50-1) is used for organic synthesis, dye manufacture, as a solvent and for other applications in chemical industry. Adverse effects of 1, 2-dichlorobenzene includes increases in liver and kidney weights and hepatotoxicity. In this study, we evaluated the genetic toxicity of 1, 2-dichlorobenzene with more advanced methods, in vitro mouse lymphoma assay $tk^{+/-}$ gene assay (MLA) and in vitro mouse supravital micronucleus (MN) assay. 1, 2-Dichlorobenzene appeared the significantly positive results and the induction of large mutant colonies only in the presence of metabolic activation system with MLA. But in vitro testing of 1, 2-dichlorobenzene yielded negative results with supravital MN assay. These results suggest that 1, 2-dichlorobenzene may play a mutagen rather than clastogen in vitro mammalian system.

Genotoxic Effects of Volatile Organic Compounds in Water (물속 휘발성 유기화합물이 염색체 돌연변이에 미치는 영향)

  • Jung Kyu Saeng;Lee Chae Yang;Shin Heuyn Kil;Lee Ki Nam;Jeung Jae Yeal;Lee Jong Young
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.16 no.5
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    • pp.899-904
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    • 2002
  • For determination of the genotoxicity of VOCs(Volatile Organic Compounds) in water, in vitro Comet assay was performed using 3T3 cells. The selected 5 VOCs; Trichloroethylene(TCE), Tetrachloroethylene(PCE), Carbontetrachloride (CteC), Dichloromethane(DCM) and Chlorofrom(Chl) and mixed solvent(Mix), are the test items for drinking water quality. Author analyzed the genotoxicity of these solvents through their tail length (TL) values. Mix, PCE, Chl, TCE in order had cytotoxicity at the highest concentration, and CCl₄ and DCM had no cytotoxic effect. TCE, CCl₄, Chl, PCE, Mix, DCM had genotoxicity, Chl, PCE, Mix had both cytotoxicity and genotoxicity simultaneously, Cytotoxic effect of mixed organic solvents, compared with that of single component, at each concentration, was influenced by the synergistic effect of the interaction of each organic component.

Antigenotoxicity of Quercetin and Its Glycosides Against Benzo(a)pyrene-induced Genotoxicity (퀘르세틴 및 퀘르세틴 배당체들의 벤조피렌에 대한 유전독성억제효과)

  • Kim, Jeong-Han;Heo, Moon-Young
    • YAKHAK HOEJI
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    • v.42 no.4
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    • pp.414-421
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    • 1998
  • In order to compare the suppressive effect of quercetin and its glycosides, such as quercitrin (quercetin-3-rhamnoside), isoquercitrin (quercetin-3-glucoside), hyperin (querceti n-3-galactoside)and rutin (quercetin-3-rhamnosyl glucoside), on the genotocicity by benzo(a)pyrene(B(a)P), in vitro sister chromatid exchange(SCE) test using mouse spleen lymphocytes and in vivo micronucleus test using mouse peripheral blood were performed. B(a)P-induced SCEs in vitro were slightly decreased by the simultaneous treatment of quercetin and its glycosides, although there was no significant decrease. On the other hand, MNU induced micronucleated reticulocytes(MNRL7s) in vivo were significantly decreased with a dose-dependent manner in all compounds tested. However, there were no differences between quercetin aglycone and glycosides in the suppressive effects under experimental condition of this study. To elucidate, the action mechanism of quercetin aglycone and its glycosides against B(a)P-induced genotoxicity, the assay of DNA binding with B(a)P was studied. Quercetin aglycone and its glycosides inhibited B(a)P metabolism in the presence of S-9 mix and decreased the B(a)P/DNA binding in the calf thymus DNA with S-9 mix. These results suggest that antigenotoxicity of quercetin antiglycosides on B(a)P-induced genotoxicity is due to decrease of DNA binding with B(a)P through the inhibition of metabolism with B(a)P in the calf thymus DNA. Therefore, quercetin and its glycosides may act as an antigenotoxicity agent and may be useful as a chemopreventive agent of polycyclic aromaic hydrocarbons like B(a)P.

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Genotoxicity Assessment of Gardenia Yellow using Short-term Assays

  • Chung, Young-Shin;Eum, Ki-Hwan;Ahn, Jun-Ho;Choi, Seon-A;Noh, Hong-June;Seo, Young-R.;Oh, Se-Wook;Lee, Michael
    • Molecular & Cellular Toxicology
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    • v.5 no.3
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    • pp.257-264
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    • 2009
  • Gardenia yellow, extracted from gardenia fruit, has been widely used as a coloring agent for foods, and thus, safety of its usage is of prime importance. In the current study, short-term genotoxicity assays were conducted to evaluate the potential genotoxic effects of gardenia yellow. The gardenia yellow used was found to contain 0.057 mg/g of genipin, a known biologically active compound of the gardenia fruit extract. Ames test did not reveal any positive results. No clastogenicity was detected by a chromosomal aberration test, even on evaluation at the highest feasible concentration of gardenia yellow. Gardenia yellow was also shown to be non-genotoxic using an in vitro comet assay and a micronucleus test with L5178Y cells, although a marginal increase in DNA damage and micronuclei frequency was reported in the respective assays. Additionally, in vivo micronucleus test results clearly demonstrated that oral administration of gardenia yellow did not induce micronuclei formation in the bone marrow cells of male ICR mice. Taken together, our results indicate that gardenia yellow is not mutagenic to bacterial cells, and that it does not cause chromosomal damage in mammalian cells, either in vitro or in vivo.

Genotoxicity Studies of DA-6034, a New Flavonoid Derivative (새로운 플라보노이드 유도체인 DA-6034에 대한 유전독성에 관한 연구)

  • 강병철;권은아;이나래;안병옥;김원배;이상구;이국현;정진호;성명훈
    • Toxicological Research
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    • v.18 no.4
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    • pp.349-354
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    • 2002
  • Inflammatory bowel disease (IBD) is a multifactorial disorder with unknown etiology and pathogenesis. Eupatilin, a kind of flavonoids, has been known to be effective for chronic diarrhea in Korea. In this study, we have investigated the genotoxicity of DA-6034, a new synthetic derivative of Eupatilin, wing in vitro and in viuo system such as Ames reverse mutation test, chromosomal aberration test and micronucleus test. in Ames reverse mutation test, DA-6034 treatment at the dose range up to 5,000 $\mu\textrm{g}$/ plate did not induced mutagenicity in Salmonella typhimurium TA98, TA100, TA102, TA1535, TA1537 with and without metabolic activation. Any significant aberration wasn't observed in chinese hamster lung(CHL) fibroblast cells treated with DA-6034 at the concentration of 5, 2.5, 1.25 mg/ml both in the absence and presence of metabolic activation system. In mouse micronucleus test, no significant increase in the occurrence of micronucleated polychromatic erythrocytes was observed in ICR male mice orally administered with DA-6034 of the doses of 2.0, 1.0, 0.5 g/kg. These results indicate that DA-6034 has no mutagenic potential under the condition in this study.

Genotoxicity Studies of STB-HO-BM, a Germanium Complex (게르마늄 복합물인 STB-HO-BM에 대한 유전독성에 관한 연구)

  • Song Si-Whan;Jung Winston;Hong Dong-Ho
    • Toxicological Research
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    • v.22 no.2
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    • pp.145-151
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    • 2006
  • We have investigated the genotoxicity of STB-HO-BM using in vitro and in vivo system such as Ames reverse mutation test, chromosomal aberration test and micronucleus test. in Ames reverse mutation test, STB-HO-BM treatment at the dose range up to 5,000 ug/plate did not induce mutagenicity in Salmonella typhimurium TA98, TA100, TA102, TA1535, TA 1537 and in Escherichia coli WP2 uvrA with and without metabolic activation. Any significant aberration wasn't observed in chinese hamster lung (CHL) fibroblast cells treated with STB-HO-BM at the concentration of 12.5, 2.5, 5 mg/ml both in the absense and presence of metabolic activation system. In mouse micrnucleus test, no significant increase in the occurrence of micronucleated polychromatic erythrocytes was observed in ICR male mice orally administered with STB-HO-BM at the doses of 0.5, 1.0, 2.0 g/kg. These results indicate that STB-HO-BM has no mutagenic potential under the condition in this study.