• 제목/요약/키워드: Genotoxic

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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.

The Evaluation of Antifungal Activities and Safeties of 6-(4-Iodophenyl)amino-7-chloro-5,8-quinolinedione (6-(4-요오도페닐)아미노-7클로로-5,8-퀴놀린디온의 항진균작용 및 안전성 평가)

  • 유충규;윤여표;허문영;이병무;강혜영;이유진
    • Journal of Food Hygiene and Safety
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    • v.14 no.1
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    • pp.55-59
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    • 1999
  • 6-(4-Iodophenyl)amino-7-chloro-5,8-quinolinedione (RCK9) was evaluated for antifungal activities. The MIC values of RCK9 were determined against A. flavus, c. albicans, C. neoformans and F. oxysporium. The RCK9 showed generally potent antifungal activities against the tested fungi. Acute oral toxicity studies of RCK9 were carried out in ICR mice of both sexes. These acute oral toxicities of RCK9 had been evaluated. RCK9 were low and LD50 values were over 2,850 mg/kg in ICR mice. The genotoxicities of RCK9 had been evaluated. RCK9 was negative in Ames test with Salmonella typhimurium and chromosomal aberration test in CHL cells. The clastogenicity was tested on the RCK9 with in vivo mouse micronucleus assay. RCK9 did not show any clastogenic effect in mouse peripheral blood and was negative in mouse micronucleus assay. The results indicate that RCK9 has no genotoxic potential under these experimental conditions.

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Assessment of Environmental Pollution with Tradescantia Bioassays (자주달개비 생물검정 기법을 이용한 환경오염 평가)

  • Kim Jin Gyu;Sin Hae Sik
    • Proceedings of the Korea Society of Environmental Biology Conference
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    • 2004.05a
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    • pp.1-15
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    • 2004
  • Higher plants can be valuable genetic assay systems for monitoring environmental pollutants and evaluating their biological toxicity. Two assays are considered ideal for in situ monitoring and testing of soil, airborne and aqueous mutagenic agents; the Tradescantia stamen hair assay for somatic cell mutations and the Tradescantia micronucleus assay for chromosome aberrations. Both assays can be used for in vivo and in vitro testing of mutagens. Since higher plant systems are now recognized as excellent indicators and have unique advantages over in situ monitoring and screening, higher plant systems could be accepted by regulatory authorities as an alternative first-tier assay system for the detection of possible genetic damages resulting from the pollutants or chemicals used and produced by industrial sectors. It has been concluded that potential mutagen and carcinogen such as the heavy metals among indoor air particulates, volatile compounds in the working places, soil, and water pollutants contribute to the overall health risk. This contribution can be considerable under certain circumstances. It is therefore important to identify the level of genotoxic activity in the environment and to relate it to the biomarkers of a health risk in humans. The results from the higher plant bioassays could make a significant contribution to assessing the risks of pollutants and protecting the public firom agents that can cause mutation anuor cancer. The plant bioassays, which are relatively inexpensive and easy to handle, are recommended for the scientists who are interested in monitoring pollutants and evaluating their environmental toxicity to living organisms.

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MICRONUCLEI INDUCTION BY REPEATED INHALATION EXPOSURE TO THE 1,1-DICHLORO-1-FLUOROETHANE BUT NOT BY THE SINGLE PERITONEAL INJECTION

  • Maeng, Seung-Hee;Chung, Hai-Won;Kim, Hyun-Young;Lim, Cheol-Hong;Lee, Jong-Yoon;Chung, Yong-Hyun;Lee, Yong-Mook;Chung, Ho-Keun;Yu, Il-Je
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.179-179
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    • 2001
  • To investigate the genotoxic effect of 1, 1-dichloro-1-fluoroethane which was widely used as a cleaning solvent at the electronic part industry, the micronucleus frequencies were recorded by examining polychromatic erythrocytes in bone marrows of single i.p. injected mice at high doses and of the repeatedly inhaled rats for 13 weeks at relatively low concentrations.(omitted)

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Toxicity and Carcinogenicity of Dichlorodiphenyltrichloroethane (DDT)

  • Harada, Takanori;Takeda, Makio;Kojima, Sayuri;Tomiyama, Naruto
    • Toxicological Research
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    • v.32 no.1
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    • pp.21-33
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    • 2016
  • Dichlorodiphenyltrichloroethane (DDT) is still used in certain areas of tropics and subtropics to control malaria and other insect-transmitted diseases. DDT and its metabolites have been extensively studied for their toxicity and carcinogenicity in animals and humans and shown to have an endocrine disrupting potential affecting reproductive system although the effects may vary among animal species in correlation with exposure levels. Epidemiologic studies revealed either positive or negative associations between exposure to DDT and tumor development, but there has been no clear evidence that DDT causes cancer in humans. In experimental animals, tumor induction by DDT has been shown in the liver, lung, and adrenals. The mechanisms of hepatic tumor development by DDT have been studied in rats and mice. DDT is known as a non-genotoxic hepatocarcinogen and has been shown to induce microsomal enzymes through activation of constitutive androstane receptor (CAR) and to inhibit gap junctional intercellular communication (GJIC) in the rodent liver. The results from our previously conducted 4-week and 2-year feeding studies of p,p'-DDT in F344 rats indicate that DDT may induce hepatocellular eosinophilic foci as a result of oxidative DNA damage and leads them to hepatic neoplasia in combination with its mitogenic activity and inhibitory effect on GJIC. Oxidative stress could be a key factor in hepatocarcinogenesis by DDT.

Influence of Genotoxic Heterocyclic Aromatic Amine Formation and Overall Mutagenicity in Ground Beef Patties Using Korean Bramble (Rubus coreanum Miquel)

  • Lee, Jae-Hwan;Shin, Han-Seung
    • Food Science and Biotechnology
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    • v.16 no.4
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    • pp.576-579
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    • 2007
  • The effects of temperature and Korean bramble (Rubus coreanum Miquel) tissue concentrate on heterocyclic aromatic amine (HAA) formation in fried ground beef patties were investigated. Various amounts of Korean bramble tissue (4.0, 7.0, and 11.0%, w/w) were added to ground beef patties were fried at 2 different temperatures (190 and $225^{\circ}C$) for 10 min/side. It was observed in the fried ground beef patties fried at $190^{\circ}C$ with the addition of 11.0%(w/w) Korean bramble that the mutagenicity decreased by 64%, and formation of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-I-methyl-6-phenylimidazo[4,5-b]-pyridine(PhIP) reduced by 55 and 86%, respectively. Although no difference in total mutagenicity was shown in patties fried at $225^{\circ}C$ with the addition of 4.0, 7.0, and 11.0%(w/w), different levels of reduction of PhIP formation in patties fried at $225^{\circ}C$ with the addition of 4.0, 7.0, and 11.0%(w/w) were shown 49, 63, and 75%, respectively.

Molecular-vased sensitivity of human leukemia cell line U937 to antineoplastic activity in a traditional medicinal plants(Selaginella tamariscina) (전통 약용 식물 권백(Selaginella tamariscina)의 항암효과에 대한 혈액 암세포주 U937의 감수성 및 그 작용기구에 대한 분자생물학적 연구)

  • 이인자;이인선;박성희
    • Journal of Food Hygiene and Safety
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    • v.11 no.1
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    • pp.71-75
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    • 1996
  • In order to study the antitumoral effect of Selaginella tamariscina extracts, the cytotoxicities to human histiocytic leukemia cells (U937) and lymphocyte were measured by MTT method. The water extract of Selaginella tamariscina was partitioned into chloroform (CHCl3), ethylacetate (EtAc), n-butanol (BuOH) and water (H2O), successively. CHCl3, EtAc and BuOH fractions of Selaginella tamariscina showed the cytotoxicity to the U937 cells but they had effect on the cytotoxicity of lymphocyte under the same conditions. The tumor-specific cytotoxicity of Selaginella tamariscina fractions migh have been attributed to their genotoxic effect on actively proliferating cells. The expression of p53 tumor suppressor gene was then evaluated by northern blotting. The increased expression of p53 was induced by Selaginella tamariscina fraction V but no expression of p53 was induced by CHCl3, EtAc, and BuOH fractions of Selaginella tamariscina water extract (fraction V) should be required for the cytotoxcity on U937 and the other fractions of Selaginella tamariscina mediated the U937 disruption.

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TATA-Binding Protein-Related Factor 2 Is Localized in the Cytoplasm of Mammalian Cells and Much of It Migrates to the Nucleus in Response to Genotoxic Agents

  • Park, Kyoung-ae;Tanaka, Yuji;Suenaga, Yusuke;Tamura, Taka-aki
    • Molecules and Cells
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    • v.22 no.2
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    • pp.203-209
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    • 2006
  • TBP (TATA-binding protein)-related factor 2 (TRF2) regulates transcription during a nuber of cellular processes. We previously demonstrated that it is localized in the cytoplasm and is translocated to the nucleus by DNA-damaging agents. However, the cytoplasmic localization of TRF2 is controversial. In this study, we reconfirmed its cytoplasmic localization in various ways and examined its nuclear migration. Stresses such as heat shock, redox agents, heavy metals, and osmotic shock did not affect localization whereas genotoxins such as methyl methanesulfonate (MMS), cisplatin, etoposide, and hydroxyurea caused it to migrate to the nucleus. Adriamycin, mitomycin C and ${\gamma}$-rays had no obvious effect. We determined optimal conditions for the nuclear migration. The proportions of cells with nuclei enriched for TRF2 were 25-60% and 5-10% for stressed cells and control cells, respectively. Nuclear translocation was observed after 1 h, 4 h and 12 h for cisplatin, etoposide and MMS and hydroxyurea, respectively. The association of TRF2 with the chromatin and promoter region of the proliferating cell nuclear antigen (PCNA) gene, a putative target of TRF2, was increased by MMS treatment. Thus TRF2 may be involved in genotoxin-induced transcriptional regulation.

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.

Use of the Comet Assay to Assess DNA Damage in Hemocytes and Gill of Oyster(Crassostrea gigas) Exposed to Pyrene and Benzo(a)pyrene (Pyrene과 Benzo(a)pyrene에 노출된 굴의 혈구세포과 아가미 세포에서의 DNA손상 측정을 위한 Comet assay의 이용)

  • 김기범;배세진
    • Journal of Aquaculture
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    • v.16 no.3
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    • pp.196-201
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    • 2003
  • Sessile organisms such as the oyster Crassostrea gigas have been given much attention as a potential biomonitoring indicator to assess the impact of toxicants on aquatic organism. In this study, we exposed cells isolated from gill of oyster (Crassostrea gigas) to hydrogen peroxide in vitro. In addition oysters were in vivo exposed to pyrene and benzo(a)pyrene at various concentrations for 2 weeks. Comet assay was used to detect DNA single strand breaks and to investigate the application of this technique as a tool for aquatic biomonitoring. Hydrogen peroxide increased DNA single strand break with increasing concentration after 30 minutes exposure in vitro. Pyrene and benzo(a)pyrene caused DNA damage only at very high concentration (100 $\mu\textrm{g}$/L or 1000 $\mu\textrm{g}$/L) at two week exposure in vivo. DNA damage was relatively higher at hemocyte than at gill. It suggested that metabolized PAHs are transferred to hemolymph from digestive gland which have a relatively high enzyme activity, and attacked the DNA of hemocyte, while gill accumulated PAHs without degrading them to their metabolites due to low enzyme activity at gill. Both in vitro and in vivo exposure experiments showed that the comet assay is an effective tool on screening whether the organism are exposed to genotoxic contaminants.