• Carbon letters
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• v.17 no.1
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• pp.45-52
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• 2016

The attachment of 2-aminobenzamide to carboxylated multi-wall carbon nanotubes (MWCNTs)-COOH was achieved through the formation of amide bonds. Then, the functionalized MWCNTs, MWCNT-amide, were treated by phosphoryl chloride to produce MWCNT-quin. The products were characterized by Fourier transform infrared spectroscopy, Raman spectroscopy, scanning electron microscopy, thermogravimetric analysis, derivative thermogravimetric, steady-state fluorescence spectroscopy, and solubility testing. MWCNT-quin showed photo-electronic properties, which is due to the attachment of the 4-hydroxyquinazoline groups to them as proved by steady-state fluorescence spectroscopy. This suggests intramolecular interactions between the tubes and the attached 4-hydroxyquinazoline. The toxicity of the samples was evaluated in human embryonic kidney HEK293 and human breast cancer SKBR3 cell lines, and the viable cell numbers were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) after the cells were cultured for 24 h. Cellular investigations showed that the modified MWCNTs, particularly MWCNT-quin, have considerably significant toxic impact on SKBR3 as compared to HEK293 at the concentration of 5 µg/mL.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.129-130
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• 1994

The science of toxicology is the understanding of the mechanisms by which exogenous agents produce deleterious effects in biological systems. The actions of chemicals such as drugs are ultimately exerted at the cellular and gene levels. Over the past decade. several in vitro alternative methods such as cultured cells for assessing the toxicity of various xenobiotics have been proposed to reduce the use of animals. In this workshop three advanced methods will be presented. These methods are novel important models for toxicologic studies. Dr. Tabuchis group has establishcd two immortalized gastric surface mucosa cell lines from the pminary cultore of gastric fundic mucosal cells of adult transgenic mice harboring a temperature sensitive simian virus 40 large T-anugen gene. As the immortalized cell lines of various tissues possess unique characteristics to maintain their normal functions for several months, these cell lines are extremely useful for not only toxicity testing but also pharmacological screening in new drug development. Professor Funatsu have studied the formation of spherical multicelluar aggregates of adult rat hepatocytes(spheroid) having tissue like structure. The sphcroid shown thre is a prototype module of an artificial liver support system. Thus, the urea synthesis activity of the artificial liver was maintained at least to days in 100％ rat blood plasma. Dr. Takezawa and his coworkers have developed a novel culture system of multicellular spheroids considered 〃organoids〃 by utilizing a thermo-responsive polymer as a substratum of anchorage dependent cells. His final goal is to reconstitute the organoids of various normal organs, e.g., liver, skin etc. and also abnormal deseased organs such as tumor.

• Toxicological Research
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• v.17
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• pp.299-304
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• 2001

Xenobiotics and their reactive intermediates bind to cellular macromolecules and/or generate oxidative stress. which provoke deleterious effects on the cell function. Induction of xenobiotic-biotrans-forming enzymes and antioxidant molecules is an important defense mechanism against such insults. A group of genes involved in the defense mechanism. e.g. genes encoding glutathione S-transferases. NAD(P)H: quinone oxidoreductase, UDP-glucuronosyltransferase (UDP-GT) and ${\gamma}$-glutamylcysteine synthetase (GGCS). have a common regulatory sequence, Antioxidant or Electrophile Responsive Element (ARE/EpRE). Recently. Nrf2. discovered as a homologue of erythroid transcription factor p45 NF-E2, was shown to bind ARE/EpRE and induce the expression of these defense genes. Mice that lack Nrf2 show low basal levels of expression and/or impaired induction of these genes. which makes the animals highly sensitive to xenobiotic toxicity. Indeed. we show here that nrf2-deficient mice had a higher mortality than did the wild-type mice when exposed to acetaminophen (APAP). Detailed analyses of APAP hepatotoxicity in the nrf2 knockout mice indicate that a large amount of reactive APAP metabolites was generated in the livers due to the impaired basal expression of two detoxifying enzyme genes, UDP-GT (Ugt1a6) and GGCS. while the cytochrome P450 content was unchanged. Thus. the studies using the nrf2 knockout mice clearly demonstrate significance of the expression of Nrf2-regulated enzymes in protection against xenobiotic toxicity.

• Microbiology and Biotechnology Letters
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• v.34 no.4
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• pp.329-334
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• 2006

Cationic liposome has been studied as one of the most promising non-viral gene delivery systems. In this report, we describe a new synthesized cholesterolic cationic lipid (2-aminoethylcarbamate-cholesterol) and dioleylphosphatidylethanolamine (DOPE) improve the cellular uptake properties of antisense ODNs, as well as plasmid DNA with low toxicity. This formulation of cholesterolic cationic lipid termed Chol-E, efficiently transfects ODNs and plasmids into many cell types in the presense or absence of 10% serum in the medium.

• International Journal of Stem Cells
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• v.17 no.2
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• pp.120-129
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• 2024

Recent amendments to regulatory frameworks have placed a greater emphasis on the utilization of in vitro testing platforms for preclinical drug evaluations and toxicity assessments. This requires advanced tissue models capable of accurately replicating liver functions for drug efficacy and toxicity predictions. Liver organoids, derived from human cell sources, offer promise as a reliable platform for drug evaluation. However, there is a lack of standardized quality evaluation methods, which hinders their regulatory acceptance. This paper proposes comprehensive quality standards tailored for liver organoids, addressing cell source validation, organoid generation, and functional assessment. These guidelines aim to enhance reproducibility and accuracy in toxicity testing, thereby accelerating the adoption of organoids as a reliable alternative or complementary tool to animal testing in drug development. The quality standards include criteria for size, cellular composition, gene expression, and functional assays, thus ensuring a robust hepatotoxicity testing platform.

• Bulletin of the Korean Chemical Society
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• v.34 no.11
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• pp.3301-3306
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• 2013

This paper aims to address the cellular toxicity of ultra-pure titanium dioxide ($TiO_2$) and zinc oxide (ZnO) nanoparticles (NPs) frequently employed in sunscreens as inorganic physical sun blockers to provide protection against adverse effects of ultraviolet (UV) radiation including UVB (290-320 nm) and UVA (320-400 nm). In consideration that the production and the use of inorganic NPs have aroused many concerns and controversies regarding their safety and toxicity and that microsized $TiO_2$ and ZnO have been increasingly replaced by $TiO_2$ and ZnO NPs (< 100 nm), it is very important to directly investigate a main problem related to the intrinsic/inherent toxicity of these NPs and/or their incompatibility with biological objects. In the present study, we took advantage of the laser-assisted method called laser ablation for generation of $TiO_2$ and ZnO NPs. NPs were prepared through a physical process of irradiating solid targets in liquid phase, enabling verification of the toxicity of ultra-pure NPs with nascent surfaces free from any contamination. Our results show that $TiO_2$ NPs are essentially non-poisonous and ZnO NPs are more toxic than $TiO_2$ NPs based on the cell viability assays.

• The Journal of the Korean bone and joint tumor society
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• v.7 no.1
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• pp.1-12
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• 2001

Purpose : To elucidate possibility of local chemotherapy from adraimycin-impregnated bone cement. Materials and Methods : Authors used 4 kinds of bone cements, Palcos R, LVC, CMW 3, Simplex P for this experimental model, included 2.5mg, 5mg, 25mg of adriamycin, respectively. We compared the differences of eluted-adriamycin concentrations between the cylindrical shape and the flat shape of bone cements, between ddH2O, 0.45% saline, 0.9% saline, and 3% saline as one of environmental conditions. Osteosarcoma cell line, Saos-2 were cultured under $37^{\circ}C$, 5% $CO_2$ in the humidified incubator with three different concentrations of adriamycinimpregnated bone cements and cellular toxicity of adriamycin eluted from bone cement was analysed according to MTT assay. Results : Authors noticed the flat shape of bone cement eluted more concentrations of adriamycin than the cyclindrical shape, bone cement immersed in 3% saline, more than 0.9% or 0.45% saline. Concentrations of adriamycin eluted from CMW 3 or Simplex R were more than Palacos R or LVC. Saos-2 were cultured with 2.5mg, 5mg, 25mg of adriamycin-impregnated bone cement, respectively, and their cellular toxicity were 95%, 98%, 99%, each. Conclusion : Adriamycin-impregnated bone cement can be one of anticancer-drug delivery sytems as possible local chemotherapy.

• Molecular & Cellular Toxicology
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• v.3 no.4
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• pp.238-245
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• 2007

Chronic formaldehyde inhalation studies have suggested its relativity to teratogenicity, cancer incidence, neurodegenerative and vascular disorders. Many toxicological data on the formaldehyde toxicity are available, but proteomic results showing complete protein profiles are limited. Therefore, alterations of protein expression patterns upon formaldehyde treatment were investigated in the human lung epithelial cell line. Differentially expressed proteins following formaldehyde treatment were analyzed on 2-dimensional gels, and further analyzed by MALDI-TOF to identify the proteins. Among the identified proteins, 24 proteins were notably up-regulated and 6 proteins were down-regulated. In particular, cytoskeleton related protein named vinculin and Rho GDP dissociation inhibitor which plays a key role in apoptosis increased remarkably.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.318.3-319
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• 2002

Peroxynitrite(ONOO-), formed from the reaction of superoxide(O2-) and nitric oxide(NO), is a potent oxidant that contributes to oxidation of various cellular constituents including lipids. amino acids, sulphydryls and nucleotides. It can cause cellular injury such as DNA fragmentation and apoptotic cell death. Also. the toxicity of ONOO- has been reported to be involved in inflammatory and nurodegenerative diseases such as Alzheimer's disease, Parkinson's disease. and atherosclerosis. (omitted)

• Korean Journal of Microbiology
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• v.29 no.1
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• pp.25-33
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• 1991

Antiviral activities of papaverine and nucleoside analogs, 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (DHPG) and acyclovir, against human cytomegalovirus (HCMV) infection were compared in vitro. Papaverine and DHPG were effective in reducing infectious HCMV yields with $ED_{50}{\s}$ (effective dose 50: the concentraion at which 50% of virus yields was obtained) of approximately 1.02 and $0.45{\mu}{\M}$, respectively; while acyclovir was less effective with an $ED_{50}$ of about $10.4{\mu}{\M}$The relative cytotoxicity of these drugs was evaluated under the same conditions used to measure infectious HCMV yields. Papaverine and DHPG demonstrated little cellular toxicity as measured by their effect on the viability of confluent cells at concentrations in the range of those demonstrating potent inhibition of HCMV replication. Similarly, protein synthesis was largely unaffected by these drugs in stationary mock-infected cells as measured by the incorporation of isotopically labelled amino acids. In contrast, cellular DNA synthesis was invariably reduced in the presence of either drug. HCMV-specific DNA synthesis was also strongly inhibited by papaverine and DHPG.