• 한국환경보건학회지
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• 제29권3호
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• pp.9-15
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• 2003

The modification of CYP2El activity is a matter of considerable interest because of its role in the metabolic activation of a variety of environmental toxicants. In the present study, the time-course of changes in human CYP2El activities was determined following treatment with solvents (acetone, dimethylsulphoxide or pyridine) using intact HepG2 cells transfected by human CYP2El. Hydroxylation of chlorzoxazone was used for the measurement of CYP2El activity. CYP2E1 protein level was increased upon cultivation of cells in the presence of the solvents for 24 hr. Determination of CYP2El activities after 24 ht cultivation with the solvents demonstrated that acetone or dimethylsulphoxide increased, whereas pyridine inhibited the activities. This differential effect of the solvents on CYP2El activities persisted to subsequent 24 ht. Competitive inhibition study suggested that pyridine has stronger binding affinity to CYP2E1 than acetone or dimethylsulphoxide. These results demonstrate that different binding affinity of the solvents to CYP2El plays important role in determining real CYP2El activity in intact cells after exposure to the solvents. Present study would be helpful in precise understanding of human CYP2El-mediated toxicity.

• Fisheries and Aquatic Sciences
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• 제12권3호
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• pp.179-184
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• 2009

Hemibarbus mylodon (Cypriniformes) is an endemic freshwater fish species in the Korean peninsula, for which urgent conservation efforts are needed. To understand their stress responses in relation to metal toxicity and thermal elevation, we performed a real-time RT-PCR-based expression assay of hepatic copper/zinc-superoxide dismutase (Cu/Zn-SOD), a key antioxidant enzyme, in response to experimental heavy metal exposure or heat treatment. The transcription of hepatic Cu/Zn-SOD was differentially modulated by acute exposure to Cu, cadmium (Cd), or Zn. Exposure to each metal at $5{\mu}M$ for 24 h revealed that Cu stimulated the mRNA expression of Cu/Zn-SOD to a greater extent than the other two heavy metals. The elevation in Cu/Zn-SOD transcripts in response to Cu exposure was dose-dependent (0.5 to $5{\mu}M$). Time course analysis of Cu/Zn-SOD expression in response to Cd exposure ($5{\mu}M$) revealed a transient pattern up to day 7. Exposure to thermal stress (an increase from 22 to $30^{\circ}C$ at a rate of $1^{\circ}C/h$ followed by $30^{\circ}C$ for 18 h) did not significantly alter SOD transcription, although heat shock protein 90 kDa (HSP90) transcription was positively correlated with an increase in temperature.

• Molecular & Cellular Toxicology
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• 제2권2호
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• pp.120-125
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• 2006

Phenytoin is an anti-epileptic. It works by slowing down impulses in the brain that cause seizures. The recent microarray technology enables us to understand possible mechanisms of genes related to compounds which have toxicity in biological system. We have studied that the effect of a compound related to hepatotoxin in vitro system using a rat whole genome microarray. In this study, we have used a rat liver epithelial cell line WB-F344 and phenytoin as a hepatotoxin. WB-F344 was treated with phenytoin for 1 to 24 hours. Total RNA was isolated at times 1, 6 and 24h following treatment of phenytoin, and hybridized to the microarray containing about 22,000 rat genes. After analysis with clustering methods, we have identified a total of 1,455 differentially expressed genes during the time course. Interestingly, about 1,049 genes exhibited differential expression pattern in response to phenytoin in early time. Therefore, the identification of genes associated with phenytoin in early response may give important insights into various toxicogenomic studies in vitro system.

• Journal of Microbiology and Biotechnology
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• 제33권1호
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• pp.106-113
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• 2023

The supply of microbiological risk-free water is essential to keep food safety and public hygiene. And removal, inactivation, and destruction of microorganisms in drinking water are key for ensuring safety in the food industry. Ultraviolet-C (UV-C) irradiation is an attractive method for efficient disinfection of water without generating toxicity and adversely affecting human health. In this study, the disinfection efficiencies of UV-C irradiation on Shigella flexneri (Gram negative) and Listeria monocytogenes (Gram positive) at various concentrations in drinking water were evaluated using a water purifier. Their morphological and physiological characteristics after UV-C irradiation were observed using fluorescence microscopy and flow cytometry combined with live/dead staining. UV-C irradiation (254 nm wavelength, irradiation dose: 40 mJ/cm²) at a water flow velocity of 3.4 L/min showed disinfection ability on both bacteria up to 10⁸ CFU/4 L. And flow cytometric analysis showed different physiological shift between S. flexneri and L. monocytogenes after UV-C irradiation, but no significant shift of morphology in both bacteria. In addition, each bacterium revealed different characteristics with time-course observation after UV-C irradiation: L. monocytogenes dramatically changed its physiological feature and seemed to reach maximum damage at 4 h and then recovered, whereas S. flexneri seemed to gradually die over time. This study revealed that UV-C irradiation of water purifiers is effective in disinfecting microbial contaminants in drinking water and provides basic information on bacterial features/responses after UV-C irradiation.

• Toxicological Research
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• 제26권4호
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• pp.293-300
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• 2010

tert-Butyl acetate (TBAc) is an organic solvent, which is commonly used in architectural coatings and industrial solvents. It has recently been exempted from the definition of a volatile organic compound (VOC) by the Air Resources Board (ARB). Since the use of TBAc as a substitute for other VOCs has increased, thus its potential risk in humans has also increased. However, its inhalation toxicity data in the literature are very limited. Hence, inhalation exposure to TBAc was carried out to investigate its toxic effects in this study. Adult male rats were exposed to TBAc for 4 h for 1 day by using a nose-only inhalation exposure chamber (low dose, $2370\;mg/m^3$ (500 ppm); high dose, $9482\;mg/m^3$ (2000 ppm)). Shamtreated control rats were exposed to clean air in the inhalation chamber for the same period. The animals were killed at 2, 7, and 15 days after exposure. At each time point, body weight measurement, bronchoalveolar lavage fluid (BALF) analysis, histopathological examination, and biochemical assay were performed. No treatment-related abnormal effects were observed in any group according to time course. Based on those findings, the median lethal concentration ($LC_{50}$) of TBAc was over $9482\;mg/m^3$ in this study. According to the MSDS, the 4 h $LC_{50}$ for TBAc for rats is over $2230\;mg/m^3$. We suggested that this value is changed and these findings may be applied in the risk assessment of TBAc which could be beneficial in a sub-acute study.

• Radiation Oncology Journal
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• 제36권2호
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• pp.103-113
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• 2018

Purpose: Anaplastic thyroid cancer (ATC) is a rare tumor with a lethal clinical course despite aggressive multimodal therapy. Intensity-modulated radiotherapy (IMRT) may achieve a good therapeutic outcome in ATC patients, and the role of IMRT should be assessed. We retrospectively reviewed outcomes for ATC treated with three-dimensional conformal radiotherapy (3D-CRT) or IMRT to determine the optimal treatment option and explore the role of radiotherapy (RT). Materials and Methods: Between December 2000 and December 2015, 41 patients with pathologically proven ATC received RT with a sufficient dose of ${\geq}40Gy$. Among them, 21 patients (51%) underwent surgery before RT. Twenty-eight patients received IMRT, and 13 received 3D-CRT. Overall survival (OS) and progression-free survival (PFS), patterns of failure, and toxicity were examined. Results: The median follow-up time for survivors was 38.0 months. The median and 1-year OS and PFS rates were 7.2 months and 29%, 4.5 months and 15%, respectively. Surgery significantly improved the prognosis (median OS: 10.7 vs. 3.9 months, p = 0.001; median PFS: 5.9 vs. 2.5 months, p = 0.007). IMRT showed significantly better PFS and OS than 3D-CRT, even in multivariate analysis (OS: hazard ratio [HR] = 0.30, p = 0.005; PFS: HR = 0.33, p = 0.005). Significantly higher radiation dose could be delivered with IMRT than 3D-CRT ($EQD2_{10}$ 66 vs. 60 Gy, p = 0.005). Only 2 patients had grade III dermatitis after IMRT. No other severe toxicity ${\geq}grade$ III occurred. Conclusion: Patients with ATC showed better prognosis through multimodal treatment. Furthermore, IMRT could achieve favorable survival rates by safely delivering higher dose than 3D-CRT.

• Radiation Oncology Journal
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• 제13권1호
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• pp.79-85
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• 1995

Purpose : To assess the efficacy of recombinant human granulocyte-macrophage colony-stimulating factor(GM-CSF) in the neutropenia by radiotherapy. Materials and Methods : Eleven patients with various solid tumor were treated with a daily subcutaneous dose of GM-CSF(3-7microgram/kg) for 5days during the radiotherapy. Before and during the course of the study all the patients were monitored by the recording of physical examination, the complete blood count with differential and reticulocyte count and liver function test. Eight patients received prior or concurrent chemotherapy. Results : In 10 patients, the neutrophilic nadir was significantly elevated and the lenght of time that Patients had a neutrophil count below $10^3/mm^3$ a threshold known to be critical to acquiring infective complications was shortened following GM-CSF injection. A significant rise (two fold or greater) of neutrophil count was seen in 10 of 11 patients. In most patients, discontinuation of GM-CSF resulted in a prompt return of granulocyte counts toward baseline. However the neutrophil count remained elevated over $10^3/mm^3$ during radiation therapy, and radiotherapy delays were avoided. Other peripheral blood components including monocytes and platelets also increased after GM-CSF treatment. No significant toxicity was encountered with subcutaneous GM-CSF treatment. Conclusion : GM-CSF was well tolerated by subcutaneous route and induced improvement in the neutropenia caused by radiotherapy.

• Journal of Microbiology and Biotechnology
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• 제21권4호
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• pp.438-447
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• 2011

Deinococcus radiodurans is extremely resistant to various genotoxic conditions and chemicals. In this study, we characterized the effect of a sublethal concentration (100 ${\mu}M$) of cadmium (Cd) on D. radiodurans using a whole-genome DNA microarray. Time-course global gene expression profiling showed that 1,505 genes out of 3,116 total ORFs were differentially expressed more than 2-fold in response to Cd treatment for at least one timepoint. The majority of the upregulated genes are related to iron uptake, cysteine biosynthesis, protein disulfide stress, and various types of DNA repair systems. The enhanced upregulation of genes involved in cysteine biosynthesis and disulfide stress indicate that Cd has a high affinity for sulfur compounds. Provocation of iron deficiency and growth resumption of Cd-treated cells by iron supplementation also indicates that CdS forms in iron-sulfur-containing proteins such as the [Fe-S] cluster. Induction of base excision, mismatch, and recombinational repair systems indicates that various types of DNA damage, especially base excision, were enhanced by Cd. Exposure to sublethal Cd stress reduces the growth rate, and many of the downregulated genes are related to cell growth, including biosynthesis of cell membrane, translation, and transcription. The differential expression of 52 regulatory genes suggests a dynamic operation of complex regulatory networks by Cd-induced stress. These results demonstrate the effect of Cd exposure on D. radiodurans and how the related genes are expressed by this stress.

• The Korean Journal of Physiology and Pharmacology
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• 제20권2호
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• pp.193-200
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• 2016

Sertraline, a selective serotonin reuptake inhibitor (SSRI), has been reported to lead to cardiac toxicity even at therapeutic doses including sudden cardiac death and ventricular arrhythmia. And in a SSRI-independent manner, sertraline has been known to inhibit various voltage-dependent channels, which play an important role in regulation of cardiovascular system. In the present study, we investigated the action of sertraline on Kv1.5, which is one of cardiac ion channels. The effect of sertraline on the cloned neuronal rat Kv1.5 channels stably expressed in Chinese hamster ovary cells was investigated using the whole-cell patch-clamp technique. Sertraline reduced Kv1.5 whole-cell currents in a reversible concentration-dependent manner, with an $IC_{50}$ value and a Hill coefficient of $0.71{\mu}M$ and 1.29, respectively. Sertraline accelerated the decay rate of inactivation of Kv1.5 currents without modifying the kinetics of current activation. The inhibition increased steeply between -20 and 0 mV, which corresponded with the voltage range for channel opening. In the voltage range positive to +10 mV, inhibition displayed a weak voltage dependence, consistent with an electrical distance ${\delta}$ of 0.16. Sertraline slowed the deactivation time course, resulting in a tail crossover phenomenon when the tail currents, recorded in the presence and absence of sertraline, were superimposed. Inhibition of Kv1.5 by sertraline was use-dependent. The present results suggest that sertraline acts on Kv1.5 currents as an open-channel blocker.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2003년도 추계국제학술대회
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• pp.174-174
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• 2003

There are many synthetic chemicals, such as di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP), used in chemical reaction processes in industry. The establishment of toxicity and detection of synthetic chemicals that may pose a genetic hazard in our enviornment is subjects of great concern at present DEHP, a ubiquitous phthalate plasticizer, induces a wide range of developmental and reproductive toxicities in mammals. DEHP belongs to the large diverse class of peroxisome proliferator compounds, which include herbicides, hypolipidemic drugs. DBP is a plasticizer used to products containing nitrocellulose, polyvinyl acetate, and polyvinyl chloride such as food wraps and blood bags. DBP is also used in cosmetics as a solvent and fixative for perfumes, a suspension agent for solids, an antifoamer, a skin emollient, and hair spray The present study was performed to examine patterns of gene expression in MCF-7 cells following DEHP and DBP exposure. Changes in gene expression were determined by microarray analysis using KISTCHIP-400 including 401 endocrine related genes based on public database and research papers. Of the genes analysis, we determined that genes detected by array showed a 2-fold or greater change in their expression level(increase or decrease). The results of this study demonstrate that a number of genes were differentially expressed in MCF-7 cells but these changes were not significant. Therefore, we keep going this study using microarray analysis and future studies will examine changes of gene expression on time-course and does treatment in variable cell lines.