• Title/Summary/Keyword: Genotoxic

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Genotoxicity Study on Khal, a Halocidin Derivative, in Bacterial and Mammalian Cells

  • Kim, Youn-Jung;Kim, Mi-Soon;Jeon, Hee-Kyoung;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.2 no.3
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    • pp.151-158
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    • 2006
  • Khal was a synthetic congener of halocidin, a heterodimeric peptide consisting of 19 and 15 amino acid residues detected in Halocynthia aurantium. This compound was considered a candidate for the development of a novel peptide antibiotic. The genotoxicity of Khal was subjected to high throughput toxicity screening (HTTS) because they revealed strong antibacterial effects. Mouse lymphoma thymidine kinase ($tk^{+/-}$) gene assay (MOLY), single cell gel electrophoresis (Comet) assay and chromosomal aberration assay in mammalian cells and Ames reverse mutation assay in bacterial system were used as simplified, inexpensive, short-term in vitro screening tests in our laboratory. These compounds are not mutagenic in S. typhimurium TA98 and TA100 strains both in the presence and absence of metabolic activation. Before performing the comet assay, $IC_{20}$ of Khal was determined the concentration of $25.51\;{\mu}/mL\;and\;21.99\;{\mu}g/mL$ with and without S-9, respectively. In the comet assay, Khal was not induced DNA damage in mouse lymphoma cell line. Also, the mutation frequencies in the Khal-treated cultures were similar to the vehicle controls. It is suggests that Khal is non-mutagenic in MOLY assay. And no clastogenicity was observed in Khal-treated Chinese hamster lung cells. The results of this battery of assays indicate that Khal has no genotoxic potential in bacterial or mammalian cell systems. Therefore, we suggest that Khal, as the optimal candidates with both no genotoxic potential and antibacterial effects must be chosen.

Genotoxicity of Total Suspended Particulate in Chuncheon Area (춘천지역 대기부유분진의 DNA 손상효과)

  • Kim, Nam-Yee;Lim, Beng-Chan;Weon, Wun-Jae;Hyun, Geun-Woo;Choi, Geum-Jong;Song, Eun-Jeong;Heo, Moon-Young
    • YAKHAK HOEJI
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    • v.51 no.6
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    • pp.415-423
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    • 2007
  • This study was to evaluate the genotoxic effects of airborne particulate matters using single cell gell elec trophoresis (comet assay) in A549 human lung carcinoma cells. The total suspended particulate (TSP) was collected on back-up filter in Chuncheon, Kangwon Do, South Korea from April, 2003 to February, 2005. The concentrations of TSP, B(a)p and most of heavy metals seemed to be higher in spring and winter, and lower in summer. And they showed higher concentration in the commercial areas and the residential area having more traffics than in the rural area. It was found that A549 cells interacting with the organic extract of TSP showed more DNA single-strand breaks compare to untreated cells. The genotoxicity of the organic extract of TSP was increased with the pre-treatment of S-9 mixture during the culture or with the treatment of endonuclease after cell lysis. The DNA damage by the organic extract of TSP was higher in winter and the commercial area than in summer and the rural area. This study suggests that TSP, heavy metals and B(a)P analyzed showed significant variation depend on the seasons and the areas which are correlated with the DNA damage evaluated by Comet assay, indicating that genotoxic biomarker is useful for toxicological evaluation of air quality.

A DNA-Damage Response Gene Expression Analysis in MCF-7 followed by γ-Radiation (MCF-7 세포주의 γ선에 의한 DNA 손상 반응 유전자 발현 양상의 분석)

  • Park Ji-Yoon;Hwang Chang-Il;Park Woong-Yang;Kim Jin-Kyu;Chai Young Gyu
    • Korean Journal of Environmental Biology
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    • v.23 no.1
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    • pp.21-26
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    • 2005
  • Cell response to genotoxic agents is complex and involves the participation of different classes of genes including cell cycle control, DNA repair and apoptosis. In this report, we presented a approach to characterize the cellular functions associated with the altered transcript profiles of MCF-7 exposed to low-dose in vitro gamma-irradiation. We used the method of human 2.4 k cDNA microarrays containing apoptosis, cell cycle, chromatin, repair, stress and chromosome genes to analyze the differential gene expression characterization that were displayed by radiation-exposed cell, human breast carcinoma MCF-7 cell line, such as 4 Gy 4 hr, 8 Gy 4 hr, and 8 Gy 12 hr. Among these genes, 66 were up-regulated and 49 were down-regulated. Specific genes were concomitantly induced in the results. Cyclin dependent kinase 4 (Cdk4) is induced for starting the cell cycle. This regulation is required for a DNA damage­induced G1 arrest. In addition to, an apoptotic pathways gene Bcl-w was concomitantly induced. Mismatch repair protein homologue-l (hMLH1), a necessary component of DNA mismatch protein repair (MMR), in G2-M cell cycle checkpoint arrest. The present study provides new information on the molecular mechanism underlying the cell response to genotoxic stress, with relevance to basic and clinical research.

Genotoxicity Studies on Carrageenan: Short-term In Vitro Assays

  • Chung, Young-Shin;Eum, Ki-Hwan;Choi, Seon-A;Oh, Se-Wook;Park, Sue-Nie;Yum, Young-Na;Kim, Joo-Hwan;Seo, Young-Rok;Lee, Michael
    • Toxicological Research
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    • v.25 no.1
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    • pp.51-58
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    • 2009
  • Carrageenan is a naturally-occurring sulfated polygalactan which has been widely used in the dairy industry and a gelling agent in non-dairy products. In this study, four short-term in vitro genotoxicity assays were investigated to evaluate the potential genotoxic effects of carrageenan. The mutagenicity of carrageenan was evaluated up to a maximum dose of 5 mg/plate in Ames test. There was no increase in the number of revertant colonies compared to its negative control at any dose in all of strains tested. To assess clastogenic effect, the in vitro chromosomal aberration assay was performed using Chinese hamster lung cells. Carrageenan was not considered to be clastogenic in this assay at up to the highest feasible concentration which could be evaluated. The in vitro comet assay and micronucleus test results obtained on L5178Y cells also revealed that carrageenan has no genotoxicity potential, although there was a marginal increase in micronuclei frequencies and DNA damage in the respective micronucleus and comet assays. Taken together, our results indicate that carrageenan was not genotoxic based on four in vitro genotoxicity results.

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.

Hygienic Quality and Safety of Gamma Irradiated Angelicae Gigantis Radix and Aloe (감마선조사에 의한 당귀와 알로에의 위생화 및 안전성 평가)

  • 강일준;이수용;이상준;김광훈;이병훈
    • Toxicological Research
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    • v.13 no.1_2
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    • pp.55-60
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    • 1997
  • Gamma irradiation was applied to Angelicae gigantis radix and Aloe to improve their hygienic quality. The effective dose of irradiation was 7 kGy in Angelicae gigantis radlx and 5 kGy in Aloe for the sterilization of all contaminated microorganisms tested. After 8 months of storage at room temperature, no growth of microorganisms was observed in the irradiated products. The safety of these products were evaluated by Salmonella typhimurium reversion assay and in vivo micronucleus assay using mouse bone marrow cells. They were negative in the bacterial reversion assay with S. typhimurium TA 98, TA100, TA1535 and TA1537. In the in vivo mouse micronucleus assay, they did not show any clastogenic effect at all doses tested. These results indicate that the gamma irradiation of Angelicae gigantis radix at 12 kGy and of Aloe at 10 kGy have no genotoxic effects under these experimental conditions.

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Use of comet assay as a bioassay in marine organisms exposed to genotoxicants (유전독성물질로 오염된 해양생물의 생물검정법으로서 comet assay 이용)

  • Kim Gi-Beum;An Joon-Gun;Kim Jae-Won
    • Journal of Environmental Science International
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    • v.14 no.11
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    • pp.1071-1079
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    • 2005
  • Using single cell gel electrophoresis, DNA single strand breaks were determined in various marine organisms. DNA damage on fish blood cells was detected to know whether there was a difference between Incheon, Pohang, Masan, and Tongyeong as a control site. Tongyeong showed the lowest DNA damage among the study areas. Mussels, transplanted to Masan Bay for one month, revealed high DNA damage at sites with high economical activity. In two weeks exposure of polychaete to Incheon sediments, higher DNA damage was detected in the sediment adjacent to Incheon harbor than open sea. These results suggested that the marine organism from the polluted area revealed a relatively high DNA damage. In addition, these areas might be contaminated with genotoxic compounds and comet assay was useful as a bioassay to detect DNA damage in marine organisms.

Genotoxic Evaluation of Gyllus bimaculatus in 3 Sets of Mutagenicity Tests

  • Ahn, Mi-Young;Bae, Hye-Jin;Lee, Byung-Mu;Ryu, Kang-Sun;Kim, Iksoo;Kim, Jin-Won
    • Proceedings of the Korean Society of Sericultural Science Conference
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    • 2003.10a
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    • pp.128-129
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    • 2003
  • Cricket (Gyilus bimacutus) is mass-bred in 6 time cycles per one year in insect farms. They are used as dry or live foods for animals, tropical fish, reptile and amphibians. Therefore, it is necessary to study the genotoxicity of whole bodies of G. bimaculatus. The aim of this present study was to evaluate the genotoxicity of the G bimaculatus extract with three methods, Ames test, chromosome aberration test in Chinese hamster ovary cells in vitro and micronucleus (MN) test in vivo which involve the different test systems (bacteria, mammalian cells and mice nuclei). (omitted)

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Genotoxicological Safety of Gamma Irradiated Salted and Fermented Shrimp (감마선조사 새우젓의 유전독성학적 안전성평가)

  • 강일준;정차권;이영숙;오성훈;변명우
    • Food Science and Preservation
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    • v.8 no.2
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    • pp.193-198
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    • 2001
  • Gamma irradiation at 20 kGy was apploed to salted and fermented shrimps to evaluate its possible genotoxicity. The genotoxicity of irradiated salted and fermented shrimps 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. 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 20 kGy-irradiated salted and fermented shrimps. These results indicate that salted and fermented shrimps irradiated at 20 kGy did not show any genotoxic effects under these experimental conditions.

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Differential Display Analysis of Gene Expression Induced under DCA Treatment in Rat Liver

  • Choi, Soon-Yong;Park, Ock-Jin
    • BMB Reports
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    • v.29 no.3
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    • pp.272-275
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    • 1996
  • The expression of genes induced by Dichloroacetate (DCA) treatment was analyzed by mRNA differential display. Purified total RNAs from rat liver treated with saline or DCA (100 mg/100 g b.w.) were reverse transcribed by using a set of oligonucleotide primers. The PCR products were resolved on a denaturing sequencing gel. PCR band representing mRNA expressed specifically in DCA-treated liver was excised and reamplified by PCR. A 120-bp c-DNA clone named IC1 was isolated and the DNA sequence of IC1 was analyzed. IC1 revealed 50% homology with 3' end of a mouse fibroblast growth factor mRNA This result indicates that DCA induces the expression of a gene which has a 50% homology with a Mouse fibroblast growth factor, and expression of this gene might be involved in non genotoxic process caused by DCA.

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