• Title/Summary/Keyword: In vitro genotoxicity

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Antigenotoxicity of Galangin and its Action Mechanism (Galangin의 유전독성 억제효과와 작용기전)

  • 허문영;류재천
    • Environmental Mutagens and Carcinogens
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    • v.18 no.2
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    • pp.77-82
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    • 1998
  • In order to compare the suppressive effect of galangin on the genotoxicity by N-methyl-N-nitrosourea (MNU) or benzo[a]pyrene B(a)P, in vivo micronycleus test using mouse peripheral blood and in vitro sister chromatid exchange(SCE) test using mouse spleen lymphocytes were performed. MNU or B(a)P-induced micronucleated reticulocytes in vivo was decreased by the simultaneous treatment of galangin. MNU or B(a)P-induced SCEs in vitro was also decreased by the simultaneous treatment of galangin. On the other hand, the determinations of [$^3$H]MNU-induced total DNA binding and methylated DNA were performed to find out the mechanism of action. [$^3$H]MNU-induced total DNA binding was inhibited by the treatment of galangin in calf thymus DNA. HPLC analysis of DNA hydrolysates showed that galangin caused a decrease of 7-methyl guanine and $O^{6}$-methyl guanine in calf thymus DNA. To elucidate the action mechanism of galangin against B(a)P, alteration of B(a)P metabolism was studied. Galangin inhibited B(a)P metabolism in the presence of S-9 mix and decreased B(a)P-DNA binding in calf thymus DNA with S-9 mix.

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Evaluation of Genotoxicity of SU-Eohyeol Pharmacopuncture Using an In Vitro Chromosome Aberration Test in Chinese Hamster Lung Cell

  • Ku, Jaseung;Hwang, Ji Hye
    • Journal of Pharmacopuncture
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    • v.25 no.3
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    • pp.290-300
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    • 2022
  • Objectives: This study was conducted to evaluate the safety of SU-Eohyeol pharmacopuncture (SUEP) by assessing its potential to cause chromosomal abnormalities in Chinese hamster lung cells (CHL/IC). Methods: A dose-curve was conducted to determine the highest dose of SUEP. Doses of 10, 5, 2.5, 1.25, 0.625, and 0.313% were used, and no cytotoxicity or SUEP precipitation was observed. SUEP doses of 10, 5, and 2.5%, with positive and negative controls, were used in a chromosome aberration test. Results: In this study, the frequency of abnormal chromosomal cells in the SUEP group did not show a statistically significant difference from that of the negative control group in short-term treatments with and without metabolic activation and the continuous treatment without metabolic activation. Compared with the negative control group, the positive control group had a significantly higher frequency of cells with structural chromosomal abnormalities. This test's results satisfied all conditions for determining the results. Conclusion: SUEP did not induce chromosomal aberrations under the conditions of this study. Other toxicity evaluations, safety studies in humans, and various clinical trials are required to evaluate the safety and efficacy of SUEP.

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 Synthetic Chemicals [XII] -in vitro Chromosomal Aberration Assay with 11 Chemicals 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.99-107
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    • 2004
  • The validation of many synthetic chemicals 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, the regulation and evaluation of the chemical hazard playa very important role to environment and human health. The clastogenicity of 11 synthetic chemicals was evaluated in Chinese hamster lung (CHL) fibroblast in vitro. Benzoyl chloride (CAS No. 98-88-4) induced chromosomal aberrations with statistical significance at the concentration of 31-123 $\mug/ml$ and 43 $\mug/ml$ in the absence and presence of S-9 metabolic activation system, respectively. 2-Propyn-l-o1 (CAS No. 107-19-7) and 2-Phenoxy ethanol (CAS No. 122-99-6) revealed clastogenicity only at the highest concentration in the presence of S-9 mixture. However, 1-naphthol (CAS No. 90-15-3) which is one of the most cytotoxic chemical among 11 chemicals tested revealed no clastogenicity both in the presence and absence of S-9 metabolic activation system. From the results of chromosomal aberration assay with 11 synthetic chemicals in CHL fibroblast in vitro, Benzoyl chloride (CAS No. 98-88-4), 2-Propyn-l-01 (CAS No. 107-19-7) and 2-Phenoxy ethanol (CAS No. 122-99-6) revealed positive clastogenic results in this study.

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Free Radical Involvement in the DNA Damaging Activity of Fumonisin Bl

  • Lee, Wan-Hee;Lee, Kil-Soo
    • Toxicological Research
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    • v.17 no.4
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    • pp.249-253
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    • 2001
  • Fumonisin B1, a mycotoxin, is thought to induce esophageal cancer in humans and apoptosis in animal cells by inhibiting ceramide synthase. Dumonisin Bl may also generate reactive oxygen species directly or indirectly, leading to DNA damage and lipid peroxidation. In this study, a DNA fragmentation assay, dichlorofluorescein (DCF) analysis, and single cell gel electrophoresis (SCGE) were used to investigate the involvement of cellular free radicals, specifically hydrogen peroxide, in the DNA damaging activity of fumonisin B1. From an in vitro DNA fragmentation assay, E. coli DNA, damage by fumonisin Bl was increased by the addition of superxide dismutase (SOD) and decreased by catalase. SCGE and DCF analysis in vivo showed that the nuclear DNA damage and intracellular free radicals in cultured rat hepatocytes treated with fumonisin B1 were increased with the concentration of fumonisin Bl . DNA damage and free radical generation were inhibited by the addition of catalase. Fumonisin Bl , in the presence of SOD, produces hydrogen peroxide causing oxidative DNA damage and protein malfunction, leading to genotoxicity and cytotoxicity of the toxin.

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Genotoxicify Studies of on Antihypertensive Agent, SKP-450 (고혈압 치료제 SKP-450의 유전독성평가)

  • 하광원;오혜영;박장환;허옥순;손수정;한의식;류근호;조용백
    • Environmental Mutagens and Carcinogens
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    • v.18 no.2
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    • pp.123-128
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    • 1998
  • To evaluate the genotoxicity of SKP-450, an antihypertensive agent the in vitro reverse mutation assay using Salmonella typhimurium, the Chromosome aberration assay using Chinese hamster lung (CHL) cells and the in vivo micronucleus assay using bone marrow cells of ddY mice were performed. In the Reverse mutation test, SKP-450 did not induced mutagenicity in Salmonella typhimurium TA 98, TA 100, TA 1535 and TA 1537 with and without metabolic activation. In the chromosome aberration assay using CHL cells, there was no increased incidence of structural and numerical aberrations with and without metabolic activation. The in vivo induction of micronuclei was measured in polychromatic erythrocytes of bone marrow of male ddY mice at 30 hours after treatment with SKP-450 by p.o once. The results showed no increased incidence of micronucleated polychromatic erythrocytes in bone marrow of ddY male mice treated with SKP-450.

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Analysis of chromosome aberration, sister chromatid exchange, micronuclei and single cell gel electrophoresis in human lymphocytes exposed in vitro to Bisphenol A and Diethylstilbestrol (비스페놀 A 및 Diethylstilbestrol의 유전독성 평가를 위한 염색체이상, 자매염색분체교환, 소핵형성, 단일세포 겔 전기영동법의 활용)

  • 김병모;정해원
    • Environmental Mutagens and Carcinogens
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    • v.21 no.2
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    • pp.135-141
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    • 2001
  • Endocrine disruptors have been implicated in carcinogenesis in animal studies, but carcinogenetic effects on human remain controversial. In order to examine the genotoxicity of two common endocrine disruptors, Bisphenol A and Diethylstilbestrol, cytogenetic endpoints including chromosome aberration (CA), sister chromatid exchange (SCE), micronuclei (MN) analyses and DNA damage by single cell gel electrophoresis (SCGE) were assessed. The effects of Bisphenol A and Diethylstilbestrol on the frequencies of CA and MN were increased in a dose-dependent manner and that of Bispheol A was more significant by Kendall'$\tau$test. Bisphenol A and Diethylstilbestrol also increased the frequency of SCE. Bisphenol A and Diethylstilbestrol induced DNA damage in a dose-dependent manner and the DNA damage induced by Diethylstilbestrol in human blood lymphocytes was more significant.

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Genotoxicity on Structural Derivatives of Sophoricoside, a Component of Sophora Japonica, in Bacterial and Mammalian Cells

  • Ryu, Jae-Chun;Kim, Youn-Jung;Kim, Mi-Soon;Kim, Min-Ji;Sarma, Sailendra Nath;Jung, Sang-Hun
    • Molecular & Cellular Toxicology
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    • v.1 no.3
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    • pp.179-188
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    • 2005
  • To develop the novel anti-allergic drug, many sophoricoside derivatives were synthesized. Among these derivatives, JSH-II-3, VI-3, VII-3, VIII-3, VII-20 and VII-20 (sodium salt) were selected and subjected to high throughput toxicity screening (HTTS) because they revealed strong IL-5 inhibitory activity and limitation of quantity. Single cell gel electrophoresis (Comet) assay, mouse lymphoma thymidine kinase ($tk^{+/-}$) gene assay (MOLY), 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. Through the primary screening using the comet assay, we could choose the first candidates of sophoricoside derivatives with no genotoxic potentials as JSH-VI-3, VII-3, VII-20 and VII-20 (sodium salt). Also JSH-VII-3, VII-20 and VII-20 (sodium salt) are non-mutagenic in MOLY assay, while JSH-II-3 is mutagenic at high concentration with the presence of metabolic activation system in both comet assay and MOLY assay. The selected derivatives (JSH-VI-3, VII-3, VII-20 and VII-20 (sodium salt) are not mutagenic in S. typhimurium TA98 and TA100 strains both in the presence and absence of metabolic activation. From results of chromosomal aberration assay, 6 h treatment of JSH-VI-3, VII-3 and VII-20 (sodium salt) were not revealed clastogenicity both in the presence and absence of S-9 mixture. Therefore, we suggests that JSH-VI-3, VII-3, VII-20 and VII-20 (sodium salt), as the optimal candidates with both no genotoxic potential and IL-5 inhibitory effects must be chosen. To process the development into new anti-inflammatory drug of these derivatives, further investigation will need.

In vitro mutagenicity and genotoxicity study of PAHs and nitro-PAHs using the bacterial revertant (Ames) test and alkaline single cell gel electrophorosis (Comet) assay

  • Kim, Soung-Ho;Oh, Seung-Min;Chung, Kyu-Hyuck
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.284.1-284.1
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    • 2002
  • In previous studies, we demonstrated that ambient PM collected from urban site of Korea air could induce DNA damage, Various mutagens and carcinogens present in the urban air differ according to the source of the pollutants. Polycyclic aromatic hydrocarbons (PAHs) and their nitrated compound are produced in the combustion of fossil fuels as diesel emission exhausts. In recent, PAH and nitro-PAH have been identified in urban air particulate matter (PM). and some of them were found to be tumorigenic in experimental animals and humans. (omitted)

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Genotoxicity of low-dose Glyphosate by Sister Chromatid Exchange (자매염색분체교환을 통한 글라이포세이트 유전독성)

  • Lee, Sang Hoon;Kim, Sung Jin;Choi, Woo Ik;Jin, Sang Chan;Choi, In Jang;Lee, Jae Ho
    • Journal of The Korean Society of Clinical Toxicology
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    • v.12 no.1
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    • pp.8-13
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    • 2014
  • Purpose: Glyphosate (N-phosphonomethyl glycine) is widely used as an herbicide for weed control in rural areas. It is also readily available for suicide attempts. Glyphosate has high toxicity and negatively affects the human body. The aim of this investigation was to study the genotoxicity of a low-concentration of glyphosate through sister chromatid exchange (SCE) in human blood lymphocytes in vitro. Methods: Primary lymphocyte cultures were obtained from blood samples of 11 males and seven females who had been exposed to glyphosate (0, 100, 200, and 300 ng/mL). The frequency of SCEs was examined and statistical analysis was performed. Results: All doses of glyphosate induced a significant dose-dependent increase in SCE frequency compared with the control group (P<0.001). In particular, the SCE frequency for exposure to low-dose glyphosate was significantly higher in females than in males. Conclusion: According to the result of this study, even a low-dose of glyphosate may damage DNA and females are more vulnerable to glyphosate.

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