• Title/Summary/Keyword: Chromosomal aberration assay

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Single Dose Oral Toxicity and Genotoxicological Safety Study of Ssanghwa-tang Fermented with Lactobacillus acidophyllus (유산균 발효 쌍화탕에 대한 단회 투여 경구 독성 및 유전 독성 연구)

  • Chung, Tae-Ho;Shim, Ki-Shuk;Kim, Dong-Seon;Lee, Jae-Hoon;Ma, Jin-Yeul
    • The Journal of Korean Medicine
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    • v.32 no.1
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    • pp.67-83
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    • 2011
  • Objectives: The purpose of this study was to examine the single dose toxicity with oral administration and genotoxicities of Ssanghwa-tang fermented with Lactobacillus acidophyllus. Materials and Methods: Clinical signs, weight changes, lethal doses$(LD_{50})$, and postmortem evaluation were determined by Globally Harmonized Classification System(GHCS) in a single-dose oral toxicity study. In vitro mammalian chromosomal aberration test was conducted with Ames test by cell proliferation suppression assessment using the cultivated CHO-K1(Chinese hamster ovary fibroblast) origins. Bacterial reversion assay was performed using Salmonella typhimurium (TA98, TA100, TA1535, and TA1537) and Escherichia coli (WP2uvrA). In vivo micronucleus test was performed using ICR mouse bone marrow. Results: No clinical sign was observed and none of the groups with doses up to 2000 mg/kg showed significant acute oral toxicity in the single dose oral administration. None of the sample doses taken during the 6 to 18 hour groups showed significant aberrant metaphases comparing to the negative control group in the in vitro mammalian chromosomal aberration test. No evidence of mutagenicity was seen for Escherichia coli (WP2uvrA) or Salmonella typhimurium (TA98, TA100, TA1535, and TA1537). No significant increase in the frequency of micronuclei was seen in the micronucleus test. Conclusion: These results indicate that the $LD_{50}$ value of Ssanghwa-Tang fermented with Lactobacillus acidophyllus may be over 2000 mg/kg and it have no acute oral toxicity and genotoxicity.

Genotoxicity and subchronic toxicological study of a novel ginsenoside derivative 25-OCH3-PPD in beagle dogs

  • Li, Wei;Zhang, Xiangrong;Ding, Meng;Xin, Yanfei;Xuan, Yaoxian;Zhao, Yuqing
    • Journal of Ginseng Research
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    • v.43 no.4
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    • pp.562-571
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    • 2019
  • Background: Ginsenosides have been widely used clinically for many years and were regarded as very safe. However, a few researches on the toxicities of these kinds of agents showed that some ginsenosides may have side-effect on the rats or dogs. So it is extremely necessary to further clarify the potential toxicity of ginsenosides. This study was carried out to investigate long-term toxicity and genotoxicity of 25-methoxydammarane-3, 12, 20-triol ($25-OCH_3-PPD$), a new derivative of ginsenoside, in beagle dogs. Methods: Twenty-four beagle dogs were divided randomly into four treatment groups and repeatedly orally administered with $25-OCH_3-PPD$ capsule at 60, 120, and 240 mg/kg/day for 91 consecutive days. Ames, micronucleus, and chromosomal aberration tests were established to analyze the possible genotoxicity of $25-OCH_3-PPD$. Results: There was no $25-OCH_3-PPD$einduced systemic toxicity in beagle dogs at any doses. The level of $25-OCH_3-PPD$ at which no adverse effects were observed was found to be 240 mg/kg/day. The result of Ames test showed that there was no significant increase in the number of revertant colonies of $25-OCH_3-PPD$ administrated groups compared to the vehicle control group. There were also no significant differences between $25-OCH_3-PPD$ administrated groups at all dose levels and negative group in the micronucleus test and chromosomal aberration assay. Conclusion: The highest dose level of $25-OCH_3-PPD$ at which no adverse effects were observed was found to be 240 mg/kg per day, and it is not a genotoxic agent either in somatic cells or germs cells. $25-OCH_3-PPD$ is an extremely safe candidate compound for antitumor treatment.

A Genotoxicological Safety Evaluation of Crude Antifungal Compounds Produced by Lactobacillus Plantarum AF1 and Lactobacillus Plantarum HD1 (Lactobacillus plantarum AF1와 Lactobacillus plantarum HD1이 생성한 조항균 물질의 유전학적 독성평가)

  • Chang, Hae-Choon;Koh, Sang-Bum;Lee, Jae-Joon
    • The Korean Journal of Community Living Science
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    • v.26 no.4
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    • pp.633-645
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    • 2015
  • This study investigates the genotoxicity of crude antifungal compounds produced by Lactobacillus plantarum AF1 (L.plantarum AF1) and Lactobacillus plantarum HD1 (L. plantarum HD1) isolated from kimchi. The genetic toxicity of crude antifungal compounds was evaluated in bacterial reverse mutation in Salmonella and Escherichia spp., chromosome aberrations in Chinese hamster lung cells, and micronucleous formations in mice. In bacterial reversion assays with Salmonella Typhimurium TA98, TA100, TA1535, TA1537, and WP2uvrA, crude antifungal compounds did not increase the number of revertant colonies in both the absence and presence of the 59 metabolic activation system. In the chromosome aberration test with Chinese hamster lung cells, crude antifungal compounds showed no increase in the frequency of chromosome aberrations in the short-period test with/without the S9 mix or in the continuos test. In the in vivo mouse micronucleus assay, crude antifungal compounds showed no increase in the frequency of polychromatic erythrocytes with micronuclei. The results show that crude antifungal compounds produced by L. plantarum AF1 and L. plantarum HD1 did not induce any genotoxicity.

Safety of Nano-sized Bee Pollen in both In-vitro and In-vivo Models (생체 외 및 생체 내 실험조건에서 나노화 벌 화분의 안전성 규명)

  • Pyeon, Hae-In;So, Soojeong;Bak, Jia;Lee, Seunghyun;Lee, Seungmin;Suh, Hwa-Jin;Lim, Je-Oh;Kim, Jung-Woo;Kim, Sun Youn;Lee, Se Ra;Lee, Yong Hyun;Chung, Il Kyung;Choi, Yun-Sik
    • Journal of Life Science
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    • v.28 no.5
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    • pp.605-614
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    • 2018
  • Bee pollen has an outer wall which is resistant to both acidic and basic solutions and even the digestive enzymes in the gastrointestinal tract. Therefore, the oral bioavailability of bee pollen is only 10-15%. A previous study reported on wet-grinding technology which increased the extraction of active ingredients from bee pollen by 11 times. This study was designed to investigate the safety of wet-ground bee pollen. First, a single dose of wet-ground bee pollen was tested in both rats and beagle dogs at dosages of 5, 10, and 20 g/kg and 1.5, 3, and 6 g/kg, respectively. In rats, compound-colored stools were found in those administered 10 g/kg or more of wet-ground bee pollen. In beagle dogs, 6 g/kg of wet-ground bee pollen induced diarrhea in one male for four hours. However, no obvious clinical signs were found through the end of the experiment in rats and beagle dogs. In addition, no histological abnormality was found in all animals. The data indicates that a single dose of up to 20 g/kg of wet-ground bee pollen is safe. Next, the genetic toxicity of nano-sized bee pollen was tested. This study employed a bacterial reverse mutation test, a micronucleus assay, and a chromosomal aberration assay. In the micronucleus assay, there was no genetic toxicity up to the dosage of 2 g/kg. There was also no genetic toxicity in the bacterial reverse mutation test and chromosomal aberration assay. This data provides important information in developing nano-sized bee pollen into more advanced functional foods and herbal medicines.

Acute Oral and Genetic Toxicity Study of ASCO EAQ80, a Novel Cationic Surfactant (투명 양이온 계면활성제 ASCO EAQ80에 대한 급성 경구 독성시험 및 유전 독성시험에 관한 연구)

  • Kim, Byeong-Jo;Kim, Dong-Hyeon;Lee, Jong-Ki;Moon, Surk-Sik
    • Applied Chemistry for Engineering
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    • v.20 no.2
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    • pp.145-153
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    • 2009
  • The acute oral and genetic toxicity of ASCO EAQ80 was established in this study. ASCO EAQ80, a novel cationic surfactant produced by Aekyung Speciality Chemicals Co. LTD. is currently commercialized as a clear fabric softener. In acute oral toxicity study, the 50% lethal dose $(LD_{50})$ of ASCO EAQ80 was determined to be higher than 5000 mg/kg and this product could be classified as Category 5 or Unclassified by Globally Harmonized Classification System. Also, to establish the gene-toxicity of ASCO EAQ80, we performed bacterial reversion assay against Salmonella typhimurium TA98, TA100, TA1535, TA1537, Escherichia coli WP2uvrA, and in vitro chromosomal aberration assay against Chinese hamster lung cells in the presence and absence of S-9 metabolic activation system. From these experiments, ASCO EAQ80 revealed nonmutagenic potential in S. typhimurium TA98, TA100, TA1535, TA1537, and Escherichia coli WP2uvrA both in the absence and presence of metabolic activation system. No clastogenicity of ASCO EAQ80 was observed in chromosomal aberration assay in vitro.

The Evaluation of Antifungal Activities and Safeties of 6-[(N-3,4-Difluorophenyl)amino]-7-Chloro-5,8-Quinolinedione (6-[(N-3,4-디플루오로페닐)아미노]-7-클로로-5,8-퀴놀린디온의 항진균작용 및 안전성 평가)

  • Yu, Chung-Gyu;Kim, Dong-Hyeon;Yun, Yeo-Pyo;Lee, Byeong-Mu;Heo, Mun-Yeong;Jeong, Hae-Mun;Gwon, Sang-Mi;Jeong, Seong-Hui
    • YAKHAK HOEJI
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    • v.40 no.5
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    • pp.608-615
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    • 1996
  • 6-[(N-3,4-Difluorophenyl)amino]-7-chloro-5,8-quinolinedione(RCK4) was tested for antifungal activities, against systemic infections with Candida albicans in normal mice. The therapeutic potential of RCK4 had been assessed in comparison with ketoconazole and fluconazole. RCK4 had $ED_{50},\;0.30{\pm}0.14$ but ketoconazole and fluconazole had $ED_{50},\;8.00{\pm}0.73,\;10.00{\pm} 0.43mg/kg$ respectively. Intraperitoneally administered RCK3 at the $ED_{50}$ for 7 days and 14 days reduced Candida albicans colony count in the kidneys and liver as well as ketoconazole and fluconazole at these $ED_{50}$. And administered RCK4 at the $ED_{50}$ for 14 days improved survival rates as well as ketoconazole. Acute oral toxicity studies of RCK4 were carried out in ICR mice of both sexes. These acute oral toxicities of RCK4 were low and $LD_{50}$ values were over 2,850mg/kg in ICR mice. The genotoxicities of RCK4 had been evaluated. RCK4 was negative in Ames test with Salmonella typhimurium and chromosomal aberration test in CHL cells. The clastogenicity was tested on the RCK4 with in vivo mouse micronucleus assay. RCK4 did not show any clastogenic effect in mouse peripheral blood and was negative in mouse micronucleus assay. These results indicate that RCK4 has no genotoxic potential under these experimental conditions.

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Genotoxicity Study of Immature Green Persimmon Extract (풋감 주정 추출물의 유전독성 연구)

  • Ham, Young-Min;Yoon, Seon-A;Hyun, Ho Bong;Go, Boram;Jung, Yong-Hwan;Oh, Dae-Ju;Yoon, Weon-Jong
    • Journal of Food Hygiene and Safety
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    • v.35 no.6
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    • pp.567-573
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    • 2020
  • The persimmon is commonly cultivated in temperate regions of the world, including China, Korea, Japan, Brazil, Turkey, and Italy. In some Asian cultures, consumers are aware of the health claims related to the persimmon and its functional ingredients. The rich phytochemistry of the persimmon has opened new avenues of research on diet-based regimens designed to cure various ailments. This study was conducted to identify the genotoxicity of immature green persimmon (Diospyros kaki THUNB.) extract (DKA). The bacterial reverse mutation assay, the chromosomal aberration assay, and the mammalian micronucleus test were performed to determine the DKA genotoxicity. The result of the bacterial reverse mutation assay revealed that the DKA did not induce mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2uvrA with or without metabolic activation of S9 mixture. The oral administration of DKA also caused no significant increase in the number of micronucleated polychromatic erythrocytes or in the mean ratio of polychromatic to total erythrocytes. In addition, DKA did not cause a significant chromosome aberration on CHL cells in the presence or absence of S9 activation. In conclusion, DKA could be considered as a reliable and safe functional food since no toxicity was found under the condition of this study.

Evaluation of Chromosomal Alteration in Electrical Workers Occupationally Exposed to Low Frequency of Electro Magnetic Field (EMFs) in Coimbatore Population, India

  • Balamuralikrishnan, Balasubramanian;Balachandar, Vellingiri;Kumar, Shanmugam Suresh;Stalin, Nattan;Varsha, Prakash;Devi, Subramaniam Mohana;Arun, Meyyazhagan;Manikantan, Pappuswamy;Venkatesan, Chinnakulandhai;Sasikala, Keshavarao;Dharwadkar, Shahnaz N.
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.6
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    • pp.2961-2966
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    • 2012
  • Extremely low frequency electro magnetic fields (EMFs) have been classified as possibly carcinogenic to humans by the International Agency for Research on Cancer. An increased number of chromosomal alterations in peripheral lymphocytes are correlated with elevated incidence of cancer. The aim of the present study was to assess occupationally induced chromosomal damage in EMF workers exposed to low levels of radiation. We used conventional metaphase chromosome aberration (CA) analysis and the micronucleus (MN) assay as biological indicators of non ionizing radiation exposure. In the present study totally 70 subjects were selected including 50 exposed and 20 controls. Informed written consent was obtained from all participants and the study was performed in accordance with the Declaration of Helsinki and the approval of the local ethical committee. A higher degree of CA and MN was observed in exposed subjects compared to controls, the frequency of CA being significantly enhanced with long years of exposure (P<0.05). Moreover increase in CA and MN with age was noted in both exposed subjects and controls, but was significantly greater in the former. The results of this study demonstrated that a significant induction of cytogenetic damage in peripheral lymphocytes of workers occupationally exposed to EMFs in electric transformer and distribution stations. In conclusion, our findings suggest that EMFs possess genotoxic capability, as measured by CA and MN assays; CA analysis appeared more sensitive than other cytogenetic end-points. It can be concluded that chronic occupational exposure to EMFs may lead to an increased risk of genetic damage among electrical workers.

The First Report to Evaluate Safety of Cyanobacterium Leptolyngbya sp. KIOST-1 for Use as a Food Ingredient: Oral Acute Toxicity and Genotoxicity Study

  • Lee, Youngdeuk;Kim, Taeho;Lee, Won-Kyu;Ryu, Yong-Kyun;Kim, Ji Hyung;Jeong, Younsik;Park, Areumi;Lee, Yeon-Ji;Oh, Chulhong;Kang, Do-Hyung
    • Journal of Microbiology and Biotechnology
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    • v.31 no.2
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    • pp.290-297
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    • 2021
  • Leptolyngbya sp. KIOST-1 (LK1) is a newly isolated cyanobacterium that shows no obvious cytotoxicity and contains high protein content for both human and animal diets. However, only limited information is available on its toxic effects. The purpose of this study was to validate the safety of LK1 powder. Following Organisation for Economic Co-operation and Development (OECD) guidelines, a single-dose oral toxicity test in Sprague Dawley rats was performed. Genotoxicity was assessed using a bacterial reverse mutation test with Salmonella typhimurium (strains TA98, TA100, TA1535, and TA1537) and Escherichia coli WP2 uvrA, an in vitro mammalian chromosome aberration test using Chinese hamster lung cells, and an in vivo mammalian erythrocyte micronucleus test using Hsd:ICR (CD-1) SPF mouse bone marrow. After LK1 administration (2,500 mg/kg), there were no LK1-related body weight changes or necropsy findings. The reverse mutation test showed no increased reverse mutation upon exposure to 5,000 ㎍/plate of the LK1 powder, the maximum tested amount. The chromosome aberration test and micronucleus assay demonstrated no chromosomal abnormalities and genotoxicity, respectively, in the presence of the LK1 powder. The absence of physiological findings and genetic abnormalities suggests that LK1 powder is appropriate as a candidate biomass to be used as a safe food ingredient.

Response of Odontoblast to the Bio-Calcium Phosphate Cement

  • Kim, Jin-Woo;Kim, Sung-Won;Kim, Gyoo-Cheon;Kim, Yong-Deok;Kim, Cheol-Hun;Kim, Bok-Joo;Kim, Uk-Kyu
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.33 no.4
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    • pp.301-307
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    • 2011
  • Purpose: If the tooth structure is damaged, then it is impossible to regenerate the tooth. The materials used to restore the tooth structure are not related to the composition of the tooth. The materials used to restore the structure can't replace the natural tooth because they just fill the defective structure. Calcium phosphate cement remineralizes the dentin and almost replaces the natural tooth, but there are some disadvantages. We conducted basic tests with Biomimetic CPC (Bio-CPC) to make sure of the possibility of the biomaterial to remineralize the defective tooth structure. Methods: In this study, the bioactivity and biocompatibility of Bio-CPC were evaluated for its potential value as the bio-material for regeneration of damaged tooth structure by conducting a cell toxicity assay (WST-1 assay), a cytokinesis-block micronucleus assay, a chromosomal aberration test, total RNA extraction and RT-PCR on MDPC-23 mouse odontoblast-like cells. Results: The in vitro cytotoxicity test showed that the Bio-CPC was fairly cytocompatible for the MDPC-23 mouse odontoblast-like cells. Conclusion: Bio-CPC has a possibility to be a new biomaterial and further study of Bio-CPC is needed.