• Molecular & Cellular Toxicology
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• 제3권4호
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• pp.267-272
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• 2007

Environmental and anthropogenic changes affect the health and stability of marine ecosystem. In this study we aimed to identify molecular biomarkers for ecotoxicological pollutants risk assessment in the rockfish (Sebastes schlegeli). We designed primers based on conserved sequences by multiple alignments of target genes from related species, and cloned the partial cDNAs of cytochrome P450 (CYP1A1), glutathione S-transferase (GST), metallothionein (MT), superoxide dismutase (SOD), ubiquitin (UB), vitellogenin (VTG) and $\beta$-actin by reverse transcription polymerase chain reaction (RT-PCR) from S. schlegeli. Northern blot results indicated that these six genes expressions were significantly induced by benzo[a]pyrene (BaP, 1 ${\mu}M$) and that the level of each of their transcripts increased in BaP-exposed rockfish in a time-dependent manner. This study suggests that transcriptional changes in these six genes may be used for monitoring environmental exposure to polycyclic aromatic hydrocarbons (PAHs).

• Molecular & Cellular Toxicology
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• 제1권1호
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• pp.52-61
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• 2005

Transcript profiling is a particularly valuable tool in the field of steroid receptor biology, as these receptors are ligand-activated transcription factors and therefore exert their initial effects through altering gene expression in responsive cells. Also, an awareness of endocrine disrupting chemicals (EDCs) and their potential screening methods to identify endocrine activity have been increased. Here we developed an in-house cDNA microarray, named KISTCHIP-400 ver. 1.0, with 416 clones, based on public database and research papers. These clones contained estrogen, androgen, thyroid hormone & receptors, sex hormone signal transduction & regulation, c-fos, c-myc, ps2 gene, metabolism related genes etc. Also, to validate the KISTCHIP-400 ver. 1.0, we investigated gene expression profiles with reference hormones, $10^{8}\;M\;17{\beta}-estradiol,\;10^{-7}\;M\;testosterone\;and\;10^{-7}\;M$ progesterone in MCF-7 cell line. As the results, gene expression profiles of three reference hormones were distinguished from each other with significant and identified 33 $17{\beta}-estradiol$ responsive genes. This study is in first step of validation for KISTCHIP-400 ver. 1.0, as following step transcriptional profile analysis on not only low concentrations of EDCs but suspected EDCs using KISTCHIP-400 ver. 1.0 is processing. Our results indicate that the developed microarray may be a useful laboratory tool for screening EDCs and elucidating endocrine disrupting mechanism.

• Molecular & Cellular Toxicology
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• 제1권1호
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• pp.40-45
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• 2005

Ursodeoxycholic acid (UDCA) has long been used as an adjuvant or first choice of therapy for liver disease. Commonly, UDCA has been reported to play a role in improving hyperbilirubinemia and disorder of bromsulphalein. More commonly, UDCA has been used in reducing the rate of cholesterol level in bile juice that can cause cholesterol stone. The effects on the promotion of bile acid release that leads an excretion of toxic materials and wastes produced in liver cells as well as various arrays of liver disease such as hepatitis. Other than already reported in clinical use, immunosuppressive effect has been studied, especially in transplantation. In the study, we hypothesized that UDCA might have a certain role in anti-inflammation through a preventive effect of pro-inflammatory potentials in the brain macrophages, microglia. We found that the treatment of $200\;{\mu}g/ml$ UDCA effectively suppressed the pro-inflammatory mediators (i.e. nitric oxide and interleukin-$1{\beta}$) in rat microglia compared to comparators. Interestingly, RT-PCR analysis suggested that UDCA strongly attenuated the expression of $IL-1{\beta}$ that was comparable with cyclosporine A at 48 h incubation. Conclusively, we found that UDCA may playa cytoprotective role in microglial cells through direct or indirect pathways by scavenging a toxic compound or an anti-inflammatory effect, which are known as major causes of neurodegenerative diseases.

• Molecular & Cellular Toxicology
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• 제1권1호
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• pp.32-39
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• 2005

Polycyclic aromatic hydrocarbons (PAHs) are an important class of environmentally prevalent xenobiotics that exert complex effects on the biological system and characterized as probably carcinogenic materials. Single cell gel electrophoresis assays were performed in order to evaluate DNA damage occurring in the T-and B lymphocytes, spleens (T/B-cell), bone marrow, and livers of mouse exposed to mixture of PAHs (Benzo(a)pyrene, Benzo(e)pyrene, Fluoranthene, Pyrene) at dose of 400, 800, or 1600 mg/kg body weight for 2 days. DNA damage of the cells purified from mice was increased in dose dependent manner. In the blood cells and organs, DNA damage was also discovered to vary directly with PAHs. Especially T-cells had been damaged more than B-cell. Plasma proteomes were separated by 2-dimensional electrophoresis with pH 4-7 ranges of IPG Dry strips and many proteins showed significant up-and -down expressions with the dose dependent manner. Of these, significant 4 spots were identified using matrix-assisted laser desorption/ionization-time of fight (MALDI-TOF) mass spectrometry. Identified proteins were related to energy metabolism and signal transduction.

• Molecular & Cellular Toxicology
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• 제4권3호
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• pp.192-198
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• 2008

A variety of titanium (Ti) and its alloys are used in the clinical procedures of bone regeneration for periodontal and dental implant therapies. This study was performed to determine the effect of different surface dental implant materials on biologic responses of a MG-63 human osteoblast-like cell line. MG-63 cells were cultured on Ti coated with hydroxyapatite (HA), calcium metaphosphate (CMP), anodized (A), which compared with non-coated Ti (control). The appearances of surface of dental implant materials and the morphology of these cells were assessed by scanning electron microscopy (SEM). The gene expression profiles of MG-63 cells cultured on Ti were examined by human cDNA microarray (1,152 elements). The expression of several genes was up- and down-regulated by different surfaces of dental implant materials. Interesting, the genes correlated with cellular adhesion and extra cellular matrix (ECM) formation were enhanced, in accordance surface morphology of the dental implant materials used.

• Molecular & Cellular Toxicology
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• 제4권3호
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• pp.205-210
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• 2008

Recent studies suggest that activated microglial cells play an essential role in the inflammatory responses and neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. This study was conducted to evaluate the protective mechanisms of Asiasarum sieboldi (AS) on LPS-induced activation of BV-2 microglial cells. The effects of AS on gene expression profiles in activated BV-2 microglial cells were evaluated using microarray analysis. BV-2 microglial cells were cultured in a 100 mm dish ($1{\times}10^7$/mL) for 24 h and then pretreated with 1 ${\mu}g$/mL AS or left untreated for 30 min. Next, 1 ${\mu}g$/mL LPS was added to the samples and the cells were reincubated at $37^{\circ}C$ for 30 min and 1 hr. The gene expression profiles of the BV-2 microglial cells varied depending on the AS. The microarray analysis revealed that MAPK signaling pathway-related genes were downregulated in AS-treated BV-2 microglial cells. AS can affect the neuroinflammatory-related pathway such as MAPK signaling pathway in activated BV-2 microglial cells.

• Molecular & Cellular Toxicology
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• 제4권3호
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• pp.218-223
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• 2008

Oxidative stress is believed to contribute to the neuronal damage induced by cerebral ischemia/reperfusion injury. The present study was undertaken to evaluate the possible antioxidant neuroprotective effect of hydroxyfullerene (a radical absorbing cage molecule) against neuronal death in hippocampal CA1 neurons following transient global cerebral ischemia in the rat. Transient global cerebral ischemia was induced in male Wistar rats by four vessel- occlusion (4VO) for 10 min. Lipid peroxidation in brain tissues was determined by measuring the concentrations of thiobarbituric acid-reactive substances (TBARS). Furthermore, the apoptotic effects of ${H_2}{O_2}$ on PC12 cells were also investigated. Cell viabilities were measured using MTT [3-(4,5-dimethylthiazolyl-2)-2,-5-diphenyltetrazolium bromide] assays. Hydroxyfullerene, when administered to rats at 0.3-3 mg/kg i.p. at 0 and 90 minutes after 4-VO was found to significantly reduce CA1 neuron death by 72.4% on hippocampal CA1 neurons. Our findings suggest that hydroxyfullerene protects neurons from transient global cerebral injury in the rat hippocampus by reducing oxidative stress and lipid peroxidation levels, which contribute to apoptotic cell death.

• Molecular & Cellular Toxicology
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• 제4권3호
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• pp.230-234
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• 2008

Epidemiological studies demonstrate an adverse effect of several environmental and occupational exposures on male sex hormone. Bisphenol A (BPA) is a weak estrogen and a widely used industrial chemical. Epoxy resin painters may be continuously exposed to BPA at high concentrations. The effect of occupational exposure of BPA on male reproduction was examined by measuring the urinary BPA, testosterone and gonadotropic hormones of epoxy resin painters in the shipyard. The painters had significantly higher concentrations of urinary BPA (2.61${\pm}$1.08 ${\mu}g$/g creatinine) than controls (1.38${\pm}$0.5 9 ${\mu}g$/g creatinine). In serum, the testosterone level of painters was significantly decreased but the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels of painters were significantly higher than controls. Occupational exposure to BPA influences testosterone and gonadotropic hormones in male workers.

• Molecular & Cellular Toxicology
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• 제4권3호
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• pp.199-204
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• 2008

The bio-molecules involved in defense mechanisms can be used as efficient biomarkers for physiological changes in organisms caused by both of internal and external stress. Thus, the expression level of genes which encoding such molecules serve as critical 'early warning system' for environmental assessment as well as health diagnosis of biological organisms. In this study, Cytochrome P450, Heat shock protein 90, Ubiquitin and ${\beta}$-actin gene were isolated for the first time from a red alga Gracilaria textorii. The quantitative differential gene expression analyses of three genes, GteCYP1A, GteHsp90 and Gte-UB, were carried out in G. textorii sporophytes collected from two different localities, polluted Sujeong (Masan, Korea) and potentially unpolluted Danggeum (Daemaemuldo Is., Korea). The transcripts of all three tested genes were highly expressed in the Sujeong population. The results suggest: 1) the Sujeong site was more polluted than the Danggeum site; 2) G. textorii could be applicable to marine environment monitoring in coastal regions.

• Molecular & Cellular Toxicology
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• 제4권2호
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• pp.132-137
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• 2008

Differential gene expression profiling was carried out in the hepatic tissue of medaka fish, Oryzias latipes, after exposure to an organophosphorus pesticide (OPP), Iprobenfos (IBP), a widely used pesticide in agri- and fish-culture, using a medaka cDNA micro array. Twenty six kinds of differentially expressed candidate genes, with 15 and 11 induced and repressed in their gene expressions, respectively, were associated with cytoskeleton (3.8%), development (7.7%), immune (7.7%), metabolism (30.8%), nucleic acid/protein binding (42.3%) and reproduction (7.7%). Of these genes, changes at the transcription level of five were re-evaluated by real-time quantitative PCR (qRT-PCR). Considering the known function of authentic genes, the effects of IBP on the biological activity and pathological aspects in medaka fish were discussed. The identified genes could be used as molecular biomarkers for biological responses to OPPs contamination in an aquatic environment.