• Biomolecules & Therapeutics
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• v.28 no.5
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• pp.381-388
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• 2020

Methamphetamine (METH) is a highly addictive psychostimulant and one of the most widely abused drugs worldwide. The continuous use of METH eventually leads to drug addiction and causes serious health complications, including attention deficit, memory loss and cognitive decline. These neurological complications are strongly associated with METH-induced neurotoxicity and neuroinflammation, which leads to neuronal cell death. The current review investigates the molecular mechanisms underlying METH-mediated neuronal damages. Our analysis demonstrates that the process of neuronal impairment by METH is closely related to oxidative stress, transcription factor activation, DNA damage, excitatory toxicity and various apoptosis pathways. Thus, we reach the conclusion here that METH-induced neuronal damages are attributed to the neurotoxic and neuroinflammatory effect of the drug. This review provides an insight into the mechanisms of METH addiction and contributes to the discovery of therapeutic targets on neurological impairment by METH abuse.

• Environmental Mutagens and Carcinogens
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• v.21 no.2
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• pp.128-134
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• 2001

Single cell gel electrophoresis (SCGE) assay, also called comet assay, is a rapid and sensitive method to detect DNA damage in single cell level. To evaluate the DNA damage of lymphocytes of pesticides sprayers, SCGE assay was carried out for 50 pesticides sprayer and 58 control subjects. They were interviewed with structured questionnaire to get the information about the kinds and amount of pesticide. Insecticides and fungicides were predominant among pesticides. Major components of pesticides were organophosphorus, organosulfate, cartap, carbamates, and triazole. Sprayed pesticides were classified into two groups. Group I included organophosphorus, organoarsenic, organotin, tetrazine, triazole and gramoxone, which were known to cause DNA damages. Group II pesticide were carbamates, surfactants, organosulfates, etc., which were not found as DNA damaging agents in scientific documents. Olive tail moments of 100 lymphocytes were measured by KOMET 3.1 program for each person. The means of tail moments were compared between farmers exposed to pesticides and control subjects. Farmers showed higher tail moments than control subjects (2.07$\pm$1.40 vs 1.53$\pm$0.77, p<0.05). The means of tail moments also were compared among group I sprayers (n=36), group II sprayers (n=24) and, control subject, and the means or tail moments were 3.4s$\pm$3.2o, 2.66$\pm$2.20 and 1.53$\pm$0.77 respectively. The difference between means of group I sprayers and controls was statistically significant (p<0.05). In conclusion, this study showed higher DNA damage in farmers exposed to pesticides than control subjects, and comet assay could be useful as a biological monitoring method of genotoxic pesticides for farmers.

• Environmental Mutagens and Carcinogens
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• v.21 no.2
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• pp.89-94
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• 2001

Recently, single cell gel electrophoresis, also known as comet assay, is widely used for the detection and measurement of DNA strand breaks in vitro and in vivo in many toxicological fields such as radiation exposure, human monitoring and toxicity evaluation. As well defined, comet assay is a sensitive, rapid and visual method for the detection of DNA strand breaks in individual cells. Briefly, a small number of damaged cells suspended in a thin agarose gel on a microscope slide were lysed, unwinded, electrophoresed, and stained with a fluorescent DNA binding dye. The electric current pulled the charged DNA from the nucleus such that relaxed and broken DNA fragments migrated further. The resulting images which were subsequently named for their appearance as comets, were measured to determine the extent of DNA damages. However, some variations could be occurred in procedures, laboratories's conditions and kind of cells used. Hence, to overcome and to harmonize these matters in comet assay, International Workshop on Genotoxicity Test Procedure (IWGTP) was held with several topics including comet assay at Washington D.C. on March, 1999. In spite of some consensus in procedures and conditions in IWGTP, there are some problems still remained to be solved. In this respect, we attempted to set the practical optimal conditions in the experimental procedures such as lysis, unwinding, electrophoresis and neutralization conditions and so on. First of all, we determined optimal lysis and unwinding time by using 150 $\mu$M methyl methanesulfonate (MMS) which is usually used concentration. And then, we determined optimal positive control concentrations of benzo(a)pyrene (BaP) and MMS in the presence and absence of S9 metabolic activation system, respectively.

• Molecular & Cellular Toxicology
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• v.1 no.2
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• pp.99-105
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• 2005

Perchloroethylene (tetrachloroethylene, PCE), a dry cleaning and degreasing solvent, can enter ground-water through accidental leak or spills. PCE can be degraded to trichloroethylene (TCE), 1, 1-dichloroethylene (DCE) and vinyl chloride (VC) as potential bio-product. These compounds have been reported that they can cause clinical diseases and cytotoxicity. However, only a little genotoxic information of these compounds has been known. In this study, we investigated DNA single strand breaks of PCE, TCE, DCE and VC by single cell gel electrophoresis assay, (comet assay) which is a sensitive, reliable and rapid method for DNA single strand breaks with mouse lymphoma L5178Y cells. From these results, $37.5\;{\mu}g/ml$ of PCE, $189\;{\mu}g/ml$ of TCE and $56.4\;{\mu}g/ml$ of DCE were revealed significant DNA damages in the absence of S-9 metabolic activation system meaning direct-acting mutagen. And in the presence of S-9 metabolic activation system, $41.5\;{\mu}g/ml$ of PCE, $328.7\;{\mu}g/ml$ of TCE and $949\;{\mu}g/ml$ of DCE were induced significant DNA damage. In the case of VC, it was revealed a significant DNA damage in the presence of S-9 metabolic activation system. Therefore, we suggest that chloroethylene compounds (PCE, TCE, DCE and VC) may be induced the DNA damage in a mammalian cell.

• The Korea Journal of Herbology
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• v.28 no.6
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• pp.79-86
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• 2013

Objectives : The purpose of this study is to investigate neuroprotective effects and molecular mechanisms of luteolin against ${\beta}$-amyloid ($A{\beta}_{25-35}$)-induced oxidative cell death in BV-2 cells. Methods : The protective effects of luteolin against $A{\beta}_{25-35}$-induced cytotoxicity and apoptotic cell death were determined by MTT dye reduction assay and TUNEL staining, respectively. The apoptotic cell death was further analyzed by measuring mitochondrial transmembrane potential and expression of pro- and/or anti-apoptotic proteins. To elucidate the molecular mechanisms underlying the protective effects of luteolin, intracellular accumulation of reactive oxygen species, oxidative damages, and expression of antioxidant enzymes were examined. Results : Luteolin pretreatment effectively attenuated $A{\beta}_{25-35}$-induced apoptotic cell death indices such as DNA fragmentation, dissipation of mitochondrial transmembrane potential, increased Bax/Bcl-2 ratio, and activation of c-Jun N-terminal kinase and caspase-3 in BV-2 cells. Furthermore, $A{\beta}_{25-35}$-induced intracellular formation of reactive oxygen species and subsequent oxidative damages such as lipid peroxidation and depletion of endogenous antioxidant glutathione were suppressed by luteolin treatment. The neuroprotective effects of luteolin might be mediated by up-regulation of cellular antioxidant defense system via up-regulation of ${\gamma}$-glutamylcysteine ligase, a rate-limiting enzyme in the glutathione biosynthesis and superoxide dismutase, an enzyme involved in dismutation of superoxide anion into oxygen and hydrogen peroxide. Conclusions : These findings suggest that luteolin has a potential to protect against $A{\beta}_{25-35}$-induced neuronal cell death and damages thereby exhibiting therapeutic utilization for the prevention and/or treatment of Alzheimer's disease.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 1996.12a
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• pp.43-43
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• 1996

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.05a
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• pp.73-73
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• 2004

• Radiation Oncology Journal
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• v.33 no.2
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• pp.66-74
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• 2015

Trace elements play crucial role in the maintenance of genome stability in the cells. Many endogenous defense enzymes are containing trace elements such as superoxide dismutase and metalloproteins. These enzymes are contributing in the detoxification of reactive oxidative species (ROS) induced by ionizing radiation in the cells. Zinc, copper, manganese, and selenium are main trace elements that have protective roles against radiation-induced DNA damages. Trace elements in the free salt forms have protective effect against cell toxicity induced by oxidative stress, metal-complex are more active in the attenuation of ROS particularly through superoxide dismutase mimetic activity. Manganese-complexes in protection of normal cell against radiation without any protective effect on cancer cells are more interesting compounds in this topic. The aim of this paper to review the role of trace elements in protection cells against genotoxicity and side effects induced by ionizing radiation.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.110-110
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• 2001

Inner shell of chestnut (Castanea Mollissima, Fagaceae) is well-known anti-wrinkle agent, which has been used for long time in the treatment of skin aging. In this study, the extract of chestnut inner shell (CMIE) and its major component, ellagic acid (EA), were studied for their protective effects against free radical generation and hydrogen peroxide-induced oxidative DNA damages in the mammalian cells.(omitted)

• Journal of Nutrition and Health
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• v.33 no.7
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• pp.717-724
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• 2000

A number of epidemiological studies has indicated lifestyles including dietary habits are closely related to the development of certain forms of cancer. These findings have led several investigators to identify the ways in which these factors mdulate the risk of cancer. Seaweeds are rich sources of non-digestible polysaccharides which possibly posses physiological functions. In vitro studies showed several components in seaweeds inhibit tumor cell growth and mutagenicity of known food mutagens. On the other hand non-digestible polysaccharides of different food sources negatively affect mineral nutrition by decreasing mineral absorption. The objectives of this study was to investigate the effect of major seaweed intake on azoxymethane(AOM) - induced DNA damage a known cancer initiation step and on apparent absorption of calcium and iron. To accomplish these objectives twenty five ICR mice were divided into five groups and fed one of the following diets for 10 days : control diet d, diet containing 10% water-soluble fraction of seamustard or seatangle diet containing 10% water-insoluble fraction of seamustard or seatangle. AOM was injected 6 hours before sacrifice and N7-methylated guanines from the colonic DNA were quantified using a gas chromatography -mass spectroscopy. Fecal samples were collected on days 4 and 8. Caclium and iron contents of the diets and feces were analyzed using an atomic absorption spectrophotometry to determine the apparent absorption of these minerals. Results are as follows. AOM-induced guanine methylation of colon was decreased in animals fed diets containing water-soluble fractions of seamustard or seatangle compared to those in animals fed control diet although only the seatnagle fed group showed statistically significant effect. Apparent calcium absorption was significantly reduced in animals fed diets containing water-insoluble fractions of seaweeds. Iron absorption was significantly decreased and negatively balanced in animals fed diets containing water-insoluble fractions of both seaweeds, and water-soluble fraction of seatangle. In conclusion, seamustard and seatangle intakes may effectively prevent colon tumorigenesis by reducing a carcinogen-induced DNA damages, and more mechanistic studies on possible role of seaweeds on carcinogenesis are required. Also, adverse effects of seaweed diets cintaming a large amount of polysaccharides on mineral nutrition should be carefully monitored.