• Journal of Ginseng Research
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• v.13 no.1
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• pp.42-48
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• 1989

The binding of bay region diol-epoxides of polycyclic aromatic hydrocarbons (PAHs) to target tissue DNA is thought to be essential for the initiation of cancer by these compounds. In this study we investigated the effect of polyacetylenes such as panaxynol and panaxydol on the formation of benzo(a)pyreno (BP)-metabolite-DNA adduct in the liver of ICR mice. Treatment of mice by i.p. administration of polyacetylenes produced a marked reduction in BP metabolite binding to DNA in vitro. Following i.v. administration of (3H)BP(300, ${\mu}$Ci/21 nmoles/0.1 nt DMSO) to mice, radioactivity was detected in the DNA of the liver in vivo. The result of tentative identification of the 4 peaks between the two standard markers for high pressure liquid chromatography showed that the peaks. I, II, III, and IV were BP-phenol oxide-DNA adduct (or BP-diol-epoxide-dCyt. adduct), (-) BP$.$diolepoxide I:dGuO adduct, (+) BP-diol-epoxide I: dGuo adduct, and BP-diol-epoxide II:dGuO adduct, respectively. The minor adduct, (-) BP-diol epoxide I: dGuo was reduced to 6971 of the amount of the control, while the major adduct, (+) BP-diolepoxide I: dGuO(peak II) which was produced from (-) BP-7, 8-diol was reduced to 78% of that of the control. The amount of the minor adduct, BP-diol-epoxide II:dGuo adduct(peak IV) which formed from (+) BP-7, 8-diol was 58% of the control. These results show that the panaxydol is more related to inhibition of the formation of the minor ad- ducts than of the major adducts, which were generally produced from ($\pm$) BP-7, 8-dihydro-dials.

• Journal of the Korean Chemical Society
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• v.55 no.1
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• pp.70-80
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• 2011

Two new palladium (II) complexes, [Pd (phen)(pip-dtc)]$NO_3$ and [Pd(phen)(mor-dtc)]$NO_3$, (where phen is 1,10-Phenantroline, pip-dtc is piperidinedithiocarbamate anion and mor-dtc is morpholinedithiocarbamate anion) have been synthesized and characterized by elemental analysis, spectroscopic studies (FT-IR, $^1H$ NMR, UV-Vis) and conductance measurement. In these complexes, the dithiocarbamate ligands coordinate with Pd (II) center as bidentate with two sulfur atoms. These two complexes have been tested against chronic myelogenous leukemia cell line, K562. They show $IC_{50}$ values less than cisplatin and thus the mode of binding of the complexes to calf thymus DNA (CT-DNA) were investigated by ultraviolet difference and fluorescence spectroscopy. They can denature DNA, exhibit cooperative binding and intercalate into DNA. Several binding and thermodynamic parameters are also described.

• Applied Biological Chemistry
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• v.27 no.4
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• pp.264-270
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• 1984

In order to obtain mutagenic data of enzymatic browning reaction products, we investigated their mutagenicity. The rec-assay with Bacillus subtilis strains $H17(rec^+)$ and $M45(rec^-)$ were carried out with their spores. Detection of double strand breakage in calf-thymus DNA was investigated into sample solution with and without $Cu^{2+}$ by the agarose slab gel electrophoresis. In the rec-assay, catechol, pyrocatechol, DL-dopa, 3,4-dihydroxytoluene, hydroquinone, hydroxyhydroquinone with and without $Cu^{2+}$ in 0.05M ana 0.1M at the enzymatic browning reaction products stowed mutagenic action. And also browning solution of 0.05M hydroxyhydroquinone and catechol with $Cu^{2+}$, hydroquinone with and without $Cu^{2+}$ of 0.1M at the enzymatic browning reaction products were strong mutagenic action. The DNA breakability of the enzymatic browning reaction products of 0.1M pyrogallol was stronger than that of 0.05M pyrogallol browning solution with $Cu^{2+}$ and 3,4-dihydroxytoluene browning solution was stronger than that of 0.01M 3,4-dihydroxytoluene browning solution.

• Proceedings of the Korean Vacuum Society Conference
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• 2015.08a
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• pp.66.1-66.1
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• 2015

Plasma medicine is an upcoming research area that has attracted the scientists to explore more deeply the utility of plasma. So, apart from the treating biomaterials and tissues with plasma, we have studied the effect of plasma with different feeding gases on modification of biomolecules. Additionally, we have checked the action of nanosecond pulsed plasma on the biomolecules. We have checked the plasma action on proteins ((Hemoglobin (Hb) Myoglobin (Mb) and lysoenzyme), calf thymus DNA and amino acids. The structural changes or structural modification of proteins and DNA have been studied using circular dichroism (CD), dynamic light scattering (DLS), gel electrophoresis, protein oxidation test, UV-vis spectroscopy and 1D NMR, while Liquid Chromatograph/Capillary Electrophoresis-Mass Spectrometer(LC/CE-MS) based qualitative bio-analysis have been used to study the modification of amino acids. We have also shown the effect of NaCl and ionic liquid on the formation of OH radicals using electron spin resonance and fluorescence techinques.

• Environmental Mutagens and Carcinogens
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• v.17 no.2
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• pp.97-108
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• 1997

The drugs or xenobiotics introduced to the body, are detoxified through the process of biotransformation in the body. In this process, most of the insoluble compounds become more polar, soluble and easily excretable. But, parts of introduced materials are metabolized to highly reactive electrophilic carcinogens through activation pathways. These metabolites are toxic and can react with DNA, RNA and proteins which are nucleophilic compounds. The objective of this study is to illustrate the aleactivation pathways of two highly reactive epoxide compounds, vinyl carbamate epoxide (VCO) and 2'-(4-nitrophenoxy)oxirane (NPO). They are the ultimate electrophilic carcinogens of ethyl carbamate(urethane) and 4-nitrophenyl vinyl ether, respectively. In this research, we studied the inhibition of the mutagenic activities of VCO or NPO by nuchieophiles [glutahione(GSH) and N-acetylcysteine(NAC)], detoxifying enzymes[epoxide hydrolase and glutathione-S-transferase(GST)] and intracellular organelles (microsomes and cytosol). In addition we also tested the suppression of DNA adducts formation by GSH and NAC. The results are summerized as follow. 1. The microsomes and cytosol which contain epoxide hydrolase and GST, respectively, decreased the mutagenicity of VCO (74% and 95%, respecfivel), and NPO (35% and 93%, respectively). The nucleophilic GSH and NAC decreased the mutagenicity by 86% (VCO) and 80% (NPO), 76% (VCO) and 40% (NPO), respectively. 2. The purified epoxide hydrolase decreased the mutagenicity of two epoxides in a dose-dependent manner, and GSH also decreased the mutagenicity in the presence of GST. 3. Formation of two DNA adducts, 7-(2'-oxoethyi)guanine (OEG) and N2,3-ethenoguanine(EG), were compared in the presence of calf thymus DNA and epoxide (VCO or NPO) in vitro system. The amounts of DNA adducts were decreased in the presence of GSH (25% and 29% in VCO, 32% and 29% in NPO), and NAC (14% and 16% in VCO, 21% and 11% in NPO), respectively. From these results, it is concluded that the ultimate carcinogenic metabolites, VCO and NPO, can be made in the body, but much of them may be inactivated and detoxified by the nucleophilic GSH, NAC and detoxifying enzymes (epoxide hydrolase and GST). Therefore, by these mechanism, the formation of DNA adducts and mutagenic activities of these two epoxides may be lowered in vivo.

• Journal of Pharmacopuncture
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• v.19 no.1
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• pp.37-44
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• 2016

Objectives: This study examined the relative efficacies of a derivative of betulinic acid (dBA) and its poly (lactide-co-glycolide) (PLGA) nano-encapsulated form in A549 lung cancer cells in vivo and in co-mutagen [sodium arsenite (SA) + benzo[a]pyrene (BaP)]-induced lung cancer in mice in vivo. Methods: dBA was loaded with PLGA nanoparticles by using the standard solvent displacement method. The sizes and morphologies of nano-dBA (NdBA) were determined by using transmission electron microscopy (TEM), and their intracellular localization was verified by using confocal microscopy. The binding and interaction of NdBA with calf thymus deoxyribonucleic acid (CT-DNA) as a target were analyzed by using conventional circular dichroism (CD) and melting temperature (Tm) profile data. Apoptotic signalling cascades in vitro and in vivo were studied by using an enzyme-linked immunosorbent assay (ELISA); the ability of NdBA to cross the blood-brain barrier (BBB) was also examined. The stage of cell cycle arrest was confirmed by using a fluorescence-activated cell-sorting (FACS) data analysis. Results: The average size of the nanoparticles was ~ 110 nm. Confocal microscopy images confirmed the presence of NdBA in the cellular cytoplasm. The bio-physical properties of dBA and NdBA ascertained from the CD and the Tm profiles revealed that NdBA had greater interaction with the target DNA than dBA did. Both dBA and NdBA arrested cell proliferation at G0/G1, NdBA showing the greater effect. NdBA also induced a greater degree of cytotoxicity in A549 cells, but it had an insignificant cytotoxic effect in normal L6 cells. The results of flow cytometric, cytogenetial and histopathological studies in mice revealed that NdBA caused less nuclear condensation and DNA damage than dBA did. TEM images showed the presence of NdBA in brain samples of NdBA fed mice, indicating its ability to cross the BBB. Conclusion: Thus, compared to dBA, NdBA appears to have greater chemoprotective potential against lung cancer.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.5 no.1
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• pp.19-32
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• 1999

To evaluate the antitumor activity and antimetastatic effects of Kamigumgusingihwan(KGSH) studies have ken done. The results were obtained as follows: 1. KGSH extracts exhibited a weak cytotoxicity against A549, SK-OV-3, B16-F10, and SK-MEL-2 cell lines. But exhibited potent cytotoxicity against P388 cell line in a dose-dependent manner. 2. The concentration inhibiting adhesion of A549, to complex extracellular matrix up to below 30% of control was recognized at $10^{-3}g/ml$ of KGSH 3. KGSH extracts showed a weak inhibitoty effect on DNA topo-isomerase I from calf thymus. 4. The T/C% was 137% in KGSH treated group in S-180 bearing ICR mice. 5. In pulmonary colonization assay, a number of colonies in the lungs were decreased significantly in KGSH treated group as compared with control group. 6. In hematological changes in B16-BL6 injected C57BL/6, numbers of WBC were decreased insignificantly in KGSH treated groups, and also those of platelet were increased insignificantly in KGSH treated groups as compared with control. 7. In CAM assay, KGSH extracts inhibited angiogenesis at $15{\mu}g/egg $concentration significantly as compared with control. Taken together these results, it is strongly demonstrated that KGSH significantly suppressed tumor metastasis by blocking cell adhesion to extracellular matrix. Therefore, KGSH is expected to be clinically a potent antimetastatic drug for the prevention and treatment of cancer.