• 한국자원식물학회지
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• 제18권1호
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• pp.169-178
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• 2005

중이온빔$(^{20}Ne)$을 담배 식물체에 조사(irradiation)하여 식물체의 생장과 DNA의 변이에 미치는 영향을 검토하였다. 발아율과 초장은 조사선 량이 증가함에 따라 감소하였다. 반면 $50Gy\~10Gy$의 저선량에서 추대와 개화가 촉진되어 발육은 오히려 촉진되었다. 총 100개의 primer를 이용하여 RAPD분석한 결과, 59개의 primer에서 총 336개의 DNA단편이 증폭되었고, 1개의 primer에서 중이온빔 조사처리구에서만 출현하는 DNA단편이 나타났다. AFLP분석 결과, 개체 특이적인 DNA단편은 나타난 반면 중이온빔 처리구 특이적인 DNA 단편은 관찰되지 않았다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권11호
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• pp.4663-4670
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• 2014

Trichostatin A (TSA) is a histone deacetylase (HDAC) inhibitor. We here investigated its effects on proliferation and apoptosis of the CNE2 carcinoma cell line, and attempted to establish genome-wide DNA methylation alteration due to differentially histone acetylation status. After cells were treated by TSA, the inhibitory rate of cell proliferation was examined with a CCK8 kit, and cell apoptosis was determined by flow cytometry. Compared to control, TSA inhibited CNE2 cell growth and induced apoptosis. Furthermore, TSA was found to induce genome-wide methylation alteration as assessed by genome-wide methylation array. Overall DNA methylation level of cells treated with TSA was higher than in controls. Function and pathway analysis revealed that many genes with methylation alteration were involved in key biological roles, such as apoptosis and cell proliferation. Three genes (DAP3, HSPB1 and CLDN) were independently confirmed by quantitative real-time PCR. Finally, we conclude that TSA inhibits CNE2 cell growth and induces apoptosis in vitro involving genome-wide DNA methylation alteration, so that it has promising application prospects in treatment of NPC in vivo. Although many unreported hypermethylated/hypomethylated genes should be further analyzed and validated, the pointers to new biomarkers and therapeutic strategies in the treatment of NPC should be stressed.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.4183-4186
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• 2012

Background: Ovarian cancer is the number one killer among all the gynecological cancers. We undertook association study to identify potential alterations in the genomic DNA of a DNA repair gene, DNA polymerase beta ($pol{\beta}$), involved in base excision repair (BER), in ovarian carcinomas of patients from Haldia, India. Mutations, splice variants have been reported earlier in different tumors other than ovarian tumors. Aim: In this study we explored the possibility of association of any mutation of $pol{\beta}$ (Exon 8) with prognosis in 152 ovarian cancer samples. Results: Alteration in the exon 8 region (Exon 8:468, $A{\rightarrow}C$; 15.1%) was noted among fifty seven polymorphism positive samples. Alteration in the intervening sequence 8 (IVS8, -25, $A{\rightarrow}C$; 3.9%) was also noted. All alterations are heterozygous in nature. Conclusions: We found no significant association among the samples from serous type, stage IV, and the $pol{\beta}$ mutations ($P{\leq}0.01$). Only a slight tendency of association was evident between IVS8, -25, A to C; and stage III. Further analysis with a larger number of samples is needed.

• KSBB Journal
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• 제11권2호
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• pp.193-200
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• 1996

DNA를 인식하여 절단하는 제한효소의 발견은 유전자를 연구, 조작할 수 있게 되어 분자생물학 연구에 큰 발전을 가져 왔다. 제한효소의 인식자리는 반 응용액의 산도, 유기용애의 소수성에 따라서 달라질 수 있다. 제한 효소 BamHI의 특이성 변화는 유기용 매의 소수성CLogP)과 산도에 직접적인 관계가 있다. 제한효소 BamHI의 인식자리의 특이성 변화는 산도 7.5에셔 LogP값이 -1.3~-1.35, 8.0에서 -1. 0 03~-2.5, 8.5에서 0.75~-2.5, 8.9에서 -0.32 ~­2 2.5 벙위에셔 각각 나타난다. 통일한 유기용매 혼합 물에서 산도가 알카리 일수록 낮은 유기용매 놓도에 서 특이성의 변화가 나타난다. DMSO용액에서 Bam H HI의 특이성 변화는 산도가 7.5일때 20% 농도에서 나타나지만 산도가 8.9일때는 4%에서 나타난다.

• 응용통계연구
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• 제24권5호
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• pp.847-859
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• 2011

cDNA microarray-based comparative genomic hybridization(CGH) data includes low-intensity spots and thus a statistical strategy is needed to detect subtle differences between different cancer classes. In this study, genes displaying a high frequency of alteration in one of the different classes were selected among the pre-selected genes that show relatively large variations between genes compared to total variations. Utilizing copy-number changes of the selected genes, this study suggests a statistical approach to predict patients' classes with increased performance by pre-classifying patients with similar genetic alteration scores. Two-stage logistic regression model(TLRM) was suggested to pre-classify homogeneous patients and predict patients' classes for cancer prediction; a decision tree(DT) was combined with logistic regression on the set of informative genes. TLRM was constructed in cDNA microarray-based CGH data from the Cancer Metastasis Research Center(CMRC) at Yonsei University; it predicted the patients' clinical diagnoses with perfect matches (except for one patient among the high-risk and low-risk classified patients where the performance of predictions is critical due to the high sensitivity and specificity requirements for clinical treatments. Accuracy validated by leave-one-out cross-validation(LOOCV) was 83.3% while other classification methods of CART and DT performed as comparisons showed worse performances than TLRM.

• 약학회지
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• 제39권6호
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• pp.689-694
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• 1995

Sphingolipids play important roles in cell regulation and signal transduction. Recently, a sphinogomyelin cycle has been described in which activation of neutral sphingomyelinase leads to the breakdown of sphingomyelin and the generation of ceramide. Ceramide, in turn, has emerged as a candidate intracellular mediator for the action of certain cell agonists and has multiple biologic actions. Ceramide is a potent suppressor of cell growth and an inducer of apoptosis. The present studies show that exposure of IM-9 cells to ceramide resulted in internucleosomal cleavage of DNA, yielding laddered patterns of oligonucleosomal fragments characteristic of apoptosis. DNA fragmentation induced by ceramide was also confirmed by diphenylamine assay. The effect of ceramide on cell cycle progression was also studied. The addition of ceramide increase G$_{1}$ phase distribution in cell cycle. Cell cycle-related cyclin D$_{1}$ gene expression was decreased in a time-dependent manner. These results suggest that apoptosis induced by ceramide is related to cell cycle associated with the alteration of cell cycle in IM-9 cells.

• 한국자기공명학회:학술대회논문집
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• 한국자기공명학회 2002년도 International Symposium on Magnetic Resonance
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• pp.11-11
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• 2002

• Environmental Engineering Research
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• 제11권5호
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• pp.277-284
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• 2006

The genetic toxicity of environmental pollutants, namely, nonylphenol (NP), bisphenol A (BPA) and chloropyriphos (CP) was investigated in aquatic sentinel species, freshwater crustacean, Daphnia magna, and larva of aquatic midge, Chironomus tentans, using Comet assay. Physiological effect of such pollutants was also investigated by studying the specimens' rates of reproduction, growth and survival. Acute toxicity results showed that, as expected, Daphnia was more sensitive than Chironomus to chemical exposure. The order of acute toxicity was CP > NP > BPA in D. magna and NP > CP > BPA in C. tentans. BPA may exert a genotoxic effect on D. magna and C. tentans, given that DNA strand breaks increased in both species exposed to this compound, whereas NP- and CP-induced DNA damage occurred only in C. tentans. In vivo genotoxic data obtained in aquatic sentinel species could provide valuable information for freshwater quality monitoring. The experiments with NP-exposed D. magna showed that the pollutant has long-term effects on reproduction, whereas no short-term effect on DNA integrity was found, being an example of a false-negative result from the biomarkers perspective. This result could be interpreted that other mechanism than genetic alteration might be involved in NP-induced reproduction failure in D. magna. False-positive results from the genotoxic biomarker obtained in BPA-exposed D. magna and in NP-exposed C. tentans make it difficult to use DNA integrity as an early warning biomarker. However, as the mere presence of genotoxic compounds, which are potentially carcinogenic, is of high concern to human and ecosystem health, it could also be important to rapidly and effectively detect genotoxic compounds in the aquatic system in ways that do not necessarily accompany a higher level of alteration. Considering the potential of D. magna and C. tentans as bioindicator species, and the importance of genotoxic biomarkers in ecotoxicity monitoring, DNA damage in these species could provide useful information for environmental risk assessment.

• The Korean Journal of Physiology and Pharmacology
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• 제23권6호
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• pp.519-528
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• 2019

Mitochondrial dysfunction is closely associated with reactive oxygen species (ROS) generation and oxidative stress in cells. On the other hand, modulation of the cellular antioxidant defense system by changes in the mitochondrial DNA (mtDNA) content is largely unknown. To determine the relationship between the cellular mtDNA content and defense system against oxidative stress, this study examined a set of myoblasts containing a depleted or reverted mtDNA content. A change in the cellular mtDNA content modulated the expression of antioxidant enzymes in myoblasts. In particular, the expression and activity of glutathione peroxidase (GPx) and catalase were inversely correlated with the mtDNA content in myoblasts. The depletion of mtDNA decreased both the reduced glutathione (GSH) and oxidized glutathione (GSSG) slightly, whereas the cellular redox status, as assessed by the GSH/GSSG ratio, was similar to that of the control. Interestingly, the steady-state level of the intracellular ROS, which depends on the reciprocal actions between ROS generation and detoxification, was reduced significantly and the lethality induced by $H_2O_2$ was alleviated by mtDNA depletion in myoblasts. Therefore, these results suggest that the ROS homeostasis and antioxidant enzymes are modulated by the cellular mtDNA content and that the increased expression and activity of GPx and catalase through the depletion of mtDNA are closely associated with an alleviation of the oxidative stress in myoblasts.

• 한국환경성돌연변이발암원학회지
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• 제18권2호
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• pp.77-82
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• 1998

In order to compare the suppressive effect of galangin on the genotoxicity by N-methyl-N-nitrosourea (MNU) or benzo[a]pyrene B(a)P, in vivo micronycleus test using mouse peripheral blood and in vitro sister chromatid exchange(SCE) test using mouse spleen lymphocytes were performed. MNU or B(a)P-induced micronucleated reticulocytes in vivo was decreased by the simultaneous treatment of galangin. MNU or B(a)P-induced SCEs in vitro was also decreased by the simultaneous treatment of galangin. On the other hand, the determinations of [$^3$H]MNU-induced total DNA binding and methylated DNA were performed to find out the mechanism of action. [$^3$H]MNU-induced total DNA binding was inhibited by the treatment of galangin in calf thymus DNA. HPLC analysis of DNA hydrolysates showed that galangin caused a decrease of 7-methyl guanine and $O^{6}$-methyl guanine in calf thymus DNA. To elucidate the action mechanism of galangin against B(a)P, alteration of B(a)P metabolism was studied. Galangin inhibited B(a)P metabolism in the presence of S-9 mix and decreased B(a)P-DNA binding in calf thymus DNA with S-9 mix.