• Title/Summary/Keyword: Toxicity screening

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Screening of toxic potential of graphene family nanomaterials using in vitro and alternative in vivo toxicity testing systems

  • Chatterjee, Nivedita;Yang, Ji Su;Park, Kwangsik;Oh, Seung Min;Park, Jeonggue;Choi, Jinhee
    • Environmental Analysis Health and Toxicology
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    • v.30
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    • pp.7.1-7.7
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    • 2015
  • Objectives The widely promising applications of graphene nanomaterials raise considerable concerns regarding their environmental and human health risk assessment. The aim of the current study was to evaluate the toxicity profiling of graphene family nanano-materials (GFNs) in alternative in vitro and in vivo toxicity testing models. Methods The GFNs used in this study are graphene nanoplatelets ([GNPs]-pristine, carboxylate [COOH] and amide [$NH_2$]) and graphene oxides (single layer [SLGO] and few layers [FLGO]). The human bronchial epithelial cells (Beas2B cells) as in vitro system and the nematode Caenorhabditis elegans as in vivo system were used to profile the toxicity response of GFNs. Cytotoxicity assays, colony formation assay for cellular toxicity and reproduction potentiality in C. elegans were used as end points to evaluate the GFNs' toxicity. Results In general, GNPs exhibited higher toxicity than GOs in Beas2B cells, and among the GNPs the order of toxicity was pristine > $NH_2$ > COOH. Although the order of toxicity of the GNPs was maintained in C. elegans reproductive toxicity, but GOs were found to be more toxic in the worms than GNPs. In both systems, SLGO exhibited profoundly greater dose dependency than FLGO. The possible reason of their differential toxicity lay in their distinctive physicochemical characteristics and agglomeration behavior in the exposure media. Conclusions The present study revealed that the toxicity of GFNs is dependent on the graphene nanomaterial's physical forms, surface functionalizations, number of layers, dose, time of exposure and obviously, on the alternative model systems used for toxicity assessment.

Assessment on combined repeated dose and reproduction/developmental toxicity of benzoyl peroxide

  • Sanghwan Song;Kim, Su-Hyon;Heekyung Bae;Lee, Moon-Soon;Park, Kwangsik
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.11b
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    • pp.171-171
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    • 2002
  • This study was carried out by an Korean GLP laboratory to assess the combined repeated dose, reproduction and developmental toxicity of benzoyl peroxide for OECD SIDS(Screening Information Data Set) program. Male and female Sprague Dawley rats were exposed to benzoyl peroxide at levels of 0, 250, 500 and 1,000 mg/kg/day for 29 days for male and for 41-51 days for female.(omitted)

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Stem Cells in Drug Screening for Neurodegenerative Disease

  • Kim, Hyun-Jung;Jin, Chang-Yun
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.1
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    • pp.1-9
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    • 2012
  • Because the average human life span has recently increased, the number of patients who are diagnosed with neurodegenerative diseases has escalated. Recent advances in stem cell research have given us access to unlimited numbers of multi-potent or pluripotent cells for screening for new drugs for neurodegenerative diseases. Neural stem cells (NSCs) are a good model with which to screen effective drugs that increase neurogenesis. Recent technologies for human embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) can provide human cells that harbour specific neurodegenerative disease. This article discusses the use of NSCs, ESCs and iPSCs for neurodegenerative drug screening and toxicity evaluation. In addition, we introduce drugs or natural products that are recently identified to affect the stem cell fate to generate neurons or glia.

Development of a Test Method for the Evaluation of DNA Damage in Mouse Spermatogonial Stem Cells

  • Jeon, Hye Lyun;Yi, Jung-Sun;Kim, Tae Sung;Oh, Youkyung;Lee, Hye Jeong;Lee, Minseong;Bang, Jin Seok;Ko, Kinarm;Ahn, Il Young;Ko, Kyungyuk;Kim, Joohwan;Park, Hye-Kyung;Lee, Jong Kwon;Sohn, Soo Jung
    • Toxicological Research
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    • v.33 no.2
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    • pp.107-118
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    • 2017
  • Although alternative test methods based on the 3Rs (Replacement, Reduction, Refinement) are being developed to replace animal testing in reproductive and developmental toxicology, they are still in an early stage. Consequently, we aimed to develop alternative test methods in male animals using mouse spermatogonial stem cells (mSSCs). Here, we modified the OECD TG 489 and optimized the in vitro comet assay in our previous study. This study aimed to verify the validity of in vitro tests involving mSSCs by comparing their results with those of in vivo tests using C57BL/6 mice by gavage. We selected hydroxyurea (HU), which is known to chemically induce male reproductive toxicity. The 50% inhibitory concentration ($IC_{50}$) value of HU was 0.9 mM, as determined by the MTT assay. In the in vitro comet assay, % tail DNA and Olive tail moment (OTM) after HU administration increased significantly, compared to the control. Annexin V, PI staining and TUNEL assays showed that HU caused apoptosis in mSSCs. In order to compare in vitro tests with in vivo tests, the same substances were administered to male C57BL/6 mice. Reproductive toxicity was observed at 25, 50, 100, and 200 mg/kg/day as measured by clinical measures of reduction in sperm motility and testicular weight. The comet assay, DCFH-DA assay, H&E staining, and TUNEL assay were also performed. The results of the test with C57BL/6 mice were similar to those with mSSCs for HU treatment. Finally, linear regression analysis showed a strong positive correlation between results of in vitro tests and those of in vivo. In conclusion, the present study is the first to demonstrate the effect of HU-induced DNA damage, ROS formation, and apoptosis in mSSCs. Further, the results of the current study suggest that mSSCs could be a useful model to predict male reproductive toxicity.

Toxicity Monitoring and Classification of Endocrine Disruptors using Bioluminescent Bacteria.

  • Min, Ji-Ho;Gu, Man-Bok
    • 한국생물공학회:학술대회논문집
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    • 2000.04a
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    • pp.117-120
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    • 2000
  • For detecting toxicity of endocrine disruptors (EDs), rapid, sensitive, and simple methods are needed. Therefore, in this study, a new method in which the different toxic effect of EDs can be monitored using 4 different recombinant bacteria was designed and evaluated. It was found that the recombinant bacteria could monitor the toxic effect, not estrogenic effect, due to EDCs through the measurement of bioluminescence and cell growth rate, which were shown to depend upon a form of cellular toxicity, such as DNA damage, protein damage, oxidative damage, and membrane damage. In addition, it was found that the damage done by EDCs can be divided into several groups based upon the toxic mechanisms of the EDCs

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Assessment of Developmental Toxicants using Human Embryonic Stem Cells

  • Hong, Eui-Ju;Jeung, Eui-Bae
    • Toxicological Research
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    • v.29 no.4
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    • pp.221-227
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    • 2013
  • Embryonic stem (ES) cells have potential for use in evaluation of developmental toxicity because they are generated in large numbers and differentiate into three germ layers following formation of embryoid bodies (EBs). In earlier study, embryonic stem cell test (EST) was established for assessment of the embryotoxic potential of compounds. Using EBs indicating the onset of differentiation of mouse ES cells, many toxicologists have refined the developmental toxicity of a variety of compounds. However, due to some limitation of the EST method resulting from species-specific differences between humans and mouse, it is an incomplete approach. In this regard, we examined the effects of several developmental toxic chemicals on formation of EBs using human ES cells. Although human ES cells are fastidious in culture and differentiation, we concluded that the relevancy of our experimental method is more accurate than that of EST using mouse ES cells. These types of studies could extend our understanding of how human ES cells could be used for monitoring developmental toxicity and its relevance in relation to its differentiation progress. In addition, this concept will be used as a model system for screening for developmental toxicity of various chemicals. This article might update new information about the usage of embryonic stem cells in the context of their possible ability in the toxicological fields.

Studies on the Brine Shrimp Toxicity of Crude Drugs (I) (수종생약의 Brine Shrimp 독성에 관한 연구(I))

  • Kim, Youn-Chul;Kim, Jeung-Hee
    • Korean Journal of Pharmacognosy
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    • v.24 no.3
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    • pp.263-265
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    • 1993
  • Brine shrimp toxicity of water extracts of twenty three crude drugs was tested by the brine shrimp bioassay. Eight crude drugs were shown to have 100% mortality in $1000{\;}{\mu}g/ml$. They were fractionated by Amberlite XAD-2 column chromatography and were tested by the brine shrimp bioassay. Methanol fraction of Rhei Rhizoma $(LC_{50}=49.60{\;}{\mu}g/ml)$ and Cantharis $(LC_{50}=54.08{\;}{\mu}g/ml)$ were shown to have potent brine shrimp toxicity in this test.

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Studies on the Population of Toxigenic Fungi in Foodstuffs - VI. Screening Tests Using HeLa Cells and Mice for Detection of Mycotoxin-Producing Fungi (한국(韓國) 식품중(食品中)의 유독성(有毒性) 진균(眞菌)에 관(關)한 연구(硏究) - VI. HeLa Cell 및 마우스를 이용(利用)한 Mycotoxin 분비균주(分泌菌株) 검색(檢索))

  • Cho, Seh-Hoon;Koh, Choon-Myung;Choi, Tae-Joo;Lew, Joon
    • The Journal of the Korean Society for Microbiology
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    • v.8 no.1
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    • pp.43-52
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    • 1973
  • Twenty culture filtrates among the various isolated strains from foodstuffs were submitted for toxicity screening using HeLa cells and mice. Fourteen strains(70%) were toxic to both HeLa cells and mice, 17 strains(85%) to HeLa cell alone and 14 strains(70%) to mice alone. As a mass screening this method employed is feasible to detect mycotoxin-producing fungi. In most instances, the results obtained by HeLa cells were in good parellelism with those obtained by mice.

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Toxicity Assessment of Gas Phase in Cigarette Smoke Using Cell-free Assay

  • Park, Chul-Hoon;Sahn, Hyung-Ok;Shin, Han-Jae;Lee, Hyeong-Seok;Min, Yaung-Keun;Hyun, Hak-Chul
    • Journal of the Korean Society of Tobacco Science
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    • v.29 no.2
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    • pp.110-117
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    • 2007
  • In vitro toxicity tests such as cytotoxicity, mutagenicity and genotoxicity assay are useful for evaluating the relative toxicity of smoke or smoke condensates obtained from different cigarette configurations. A major disadvantage of these tests is relatively time-consuming, complicated and expensive. Recently, a cell-free glutathione consumption assay (GCA) as a rapid and simple screening method for the toxicity assessment of smoke has been reported by Cahours et al. (CORESTA, 2006). This study was carried out to assess the GCA application capable of predicting the toxicity of gas/vapor phase (GVP) of cigarette smoke and to identify individual compounds responsible for the glutathione (GSH) consumption in smoke. Each GVPs from 2R4F, standard cigarette, carbon filter cigarette (ExC) and new carbon filter cigarette (ExN), test cigarettes were collected by automatic smoking machine and evaluated the relative toxicity by GCA and neutral red uptake (NRU) assay. Toxic compounds existed in smoke were also chosen, relative toxicities of these compounds were screened by using two methods and compared individually. The overall order of toxicity by GCA was 2R4F > ExC > ExN, which was consistent with the result of Neutral Red Uptake assay. The levels of carbonyl compounds of ExN were lower than those of 2R4F and ExC, indicating that GSH consumption was associated with carbonyl compound yields. A major toxicant under current study is acrolein, which contributed to more than half of the GSH consumption. Collectively, the toxicity of GVP determined by GCA method may be mainly attributed to acrolein.

Sol-gel Material Optimization for Aptamer Biosensors

  • Ahn, Ji-Young;Cho, Min-Jung;Lee, Se-Ram;Park, Jun-Tae;Hong, Seok-Jin;Shin, Sung-Ho;Jeong, Min-Ku;Lee, Dong-Ki;Kim, So-Youn
    • Molecular & Cellular Toxicology
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    • v.4 no.2
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    • pp.100-105
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    • 2008
  • Biochips are a powerful emerging technology for biomedical, environmental applications. Especially, making use of bioseonors in the evaluation of toxicity becomes increasingly important. For biosensor as a toxicity detection, biomolecules like antibodies or aptamers have been developed to specifically capture the toxic target molecules. In addition, the development of optimal chip materials capable of maintaining the activity of embedded biomolecules such as proteins or aptamers has proven challenging. Here, using sol-gel materials, new chip material, whose ability for immobilizing the embedded aptamers and maintaining the ability of embedded aptamers is optimal, was searched. We used sol-gel formulation screening methods previously developed and found the best formulation which shows high sensitive and specific interactions of aptamers. This study results will support the technological advancement for diagnosis and environmental sensor.