• Toxicological Research
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• 제7권2호
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• pp.157-163
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• 1991

The effect of patulin, a mycotoxin, on the growth of Escherichia coli cell was investigated. E. coli cell elongation usually shown in SOS-response for DNA repair was induced by 20 mg of patulin per ml. After staining the E. coli chromosome with fluorescence dye(DAPI, 4', 6-diamino-2-phenyl-indole), chromosomal DNA partitioning was not affected by patulin. The observation indicateds that patulin acts as a DNA damaging agent which is effective for E. coli cell elongation introduced by the inhibition of septum formation.

• Toxicological Research
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• 제29권1호
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• pp.43-52
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• 2013

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium that are found in cereals and agricultural products. ZEN has been implicated in mycotoxicosis in farm animals and in humans. The toxic effects of ZEN are well known, but the ability of an alkaline Comet assay to assess ZEN-induced oxidative DNA damage in Chang liver cells has not been established. The first aim of this study was to evaluate the Comet assay for the determination of cytotoxicity and extent of DNA damage induced by ZEN toxin, and the second aim was to investigate the ability of N-acetylcysteine amide (NACA) to protect cells from ZEN-induced toxicity. In the Comet assay, DNA damage was assessed by quantifying the tail extent moment (TEM; arbitrary unit) and tail length (TL; arbitrary unit), which are used as indicators of DNA strand breaks in SCGE. The cytotoxic effects of ZEN in Chang liver cells were mediated by inhibition of cell proliferation and induction of oxidative DNA damage. Increasing the concentration of ZEN increased the extent of DNA damage. The extent of DNA migration, and percentage of cells with tails were significantly increased in a concentration-dependent manner following treatment with ZEN toxin (p < 0.05). Treatment with a low concentration of ZEN toxin (25 ${\mu}M$) induced a relatively low level of DNA damage, compared to treatment of cells with a high concentration of ZEN toxin (250 ${\mu}M$). Oxidative DNA damage appeared to be a key determinant of ZEN-induced toxicity in Chang liver cells. Significant reductions in cytolethality and oxidative DNA damage were observed when cells were pretreated with NACA prior to exposure to any concentration of ZEN. Our data suggest that ZEN induces DNA damage in Chang liver cells, and that the antioxidant activity of NACA may contribute to the reduction of ZEN-induced DNA damage and cytotoxicity via elimination of oxidative stress.

• Toxicological Research
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• 제7권1호
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• pp.83-92
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• 1991

Complexities of testis structure and function are emphasized in morphometrical and genotoxic evaluation by statistical analysis. F-344 rats were treated with azinphos methyl, cyclophosphomide, and dichlorvos. And Brdu was injected with intrapertionially before sacrifice. The existence and degree of DNA damage were measured by Brdu labeling index which represented relative amount of Brdu incorporated in DNA, morphometric change was evaluated by the relative length of tubular diameter in circular seminiferous tubules and the number of spermatogonia per Sertoli cell in stage IX seminiferous tubules.

• Journal of Applied Biological Chemistry
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• 제56권1호
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• pp.37-42
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• 2013

In eukaryotes, most of the genome are transcribed, however only a small proportion of total transcripts encodes for protein, thus resulting in many of noncoding RNAs. In order to recover DNA damage including DNA double-strand breaks (DSBs) eukaryotes have evolved complex mechanisms and these are processed through coordinated mechanisms of protein sensors, transducers, and effectors including RNAs. During recent years, small RNAs have been increasingly studied and gradually considered as key regulators in various aspects of biology. Upon DNA damage, small RNAs including diRNAs (DSB induced RNA) are generated in both plant and human cell lines. Inhibition of their biogenesis has severe influence on DSB repair system.

• 약학회지
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• 제39권1호
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• pp.94-101
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• 1995

In order to evaluate the suppressive effects of galangin on the DNA damage induced by N-methyl-N-nitrosourea(MNU), in vitro sister chromatid exchange(SCE) test using Chinese Hamster ovary(CHO) cells was performed. Also the determinations of [$^{3}$H] MNU-induced total DNA binding and methylated DNA were performed to find out the mechanism of action by galangin. MNU-induced SCEs were significantly decreased by simultaneous and pretreatment of galangin when S-9 mix was added only. In post-treatment, however, the MNU-induced SCEs were not decreased when S-9 mix was added or not. [$^{3}$H] MNU-induced total DNA binding was significantly inhibited by the treatment of galangin in calf thymus DNA and CHO cells. HPLC analysis of DNA hydrolysates shows that galangin caused a dose-dependant decrease in calf thymus DNA, but not significant decrease in CHO cells. These results suggest that the inhibition of galangin on the MNU-induced SCEs is due to the decrease of DNA binding and methylation with MNU. Therefore, galangin may be useful as a chemopreventive agent of alkylating agents.

• Journal of Applied Biological Chemistry
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• 제61권2호
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• pp.109-117
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• 2018

최근까지도, 현대사회의 암 발생률은 급격하게 증가하고 있다. 인체 내부에서 내재적 또는 외재적인 요인에 의해 DNA 손상이 발생되고, 세포는 DNA 손상에 대한 방어기작을 통해 스스로를 방어한다. 또한, 비정상적인 DNA 생성 및 결손된 DNA 가닥의 복원은 노화, 암, 염증 등 다양한 질병으로부터 기인한다. 많은 연구자는 이러한 DNA 손상을 억제하기 위하여 적절한 소재 탐색에 많은 관심을 두고 있으며, 특히 합성화합물의 부작용이 알려지면서, 천연물을 기반으로 한 암 예방적 소재에 대한 연구가 많이 이루어지고 있다. 토복령은 백합과(Liliacese)에 속하는 청미래덩굴(Smilax china L.)의 근경이며, 전통적으로 해독과 종기 등의 치료제로 사용되어왔다. 하지만 토복령의 DNA 손상에 대한 억제 효과에 대한 연구는 미흡하다. 본 논문에서는 토복령의 항산화 효과 및 DNA 손상에 대한 억제 효과를 확인하고, 식물이 포함하는 phenolic 화합물의 활성과 연관 관계를 확인하고자 하였다. 항산화 효과를 확인하기 위해, DPPH 라디칼 및 ABTS 라디칼에 대한 소거 활성을 확인하였다. 토복령 추출물은 DPPH 및 ABTS 라디칼을 효과적으로 제거하였으며, 높은 환원력을 나타냈다. HPLC 분석을 통해 phenolic 화합물을 정량 및 동정하였으며, 항산화 효과와 phenolic 화합물의 연관 관계를 확인하였다. 또한, $OH^-$ 라디칼 및 $Fe^{2+}$으로 유발된 plasmid DNA 손상에 대한 방어 효과를 확인하였다. 세포 수준에서, DNA 손상에 대한 저해 효과는 산화적 스트레스로 유발된 NIH 3T3 세포의 ${\gamma]$-H2AX 및 p53 단백질 발현 저해 활성을 확인하였다. 또한, H2AX 및 p53 mRNA 수준의 저해 활성을 확인하였다. 결론적으로, 토복령 추출물의 phenolic 화합물의 항산화 효과 및 DNA 손상에 대한 억제 효과를 확인하였다.

• Animal cells and systems
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• 제6권3호
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• pp.263-269
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• 2002

The p53 tumor suppressor gene is among the most frequently mutated and studied genes in human cancer, but the mechanisms by which it sur presses tumor formation remain unclear. DNA damage regulates both the protein levels of p53 and its affinity for specific DNA sequences. Stabilization of p53 in response to DNA damage is caused by its dissociation from Mdm2, a downstream target gene of p53 and a protein that targets p53 for degradation in the proteosome. Recent studies have suggested that phosphorylation of human p53 at Ser20 is important for stabilizing p53 in response to DNA damage through disruption of the interaction between Mdm2 and p53. We generated mice with an allele encoding changes at Ser20, known to be essential for p53 accumulation following DNA damage, to enable analyses of p53 stabilization in vivo. Our data showed that the mutant p53 was clearly defective for full stabilization of p53 in response to DNA damage. We concluded that Ser20 phosphorylation is critical for modulating the negative regulation of p53 by Mdm2, probably through phosphorylation-dependent inhibition of p53-Mdm2 interaction in the physiological context.

• The Korean Journal of Physiology and Pharmacology
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• 제17권4호
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• pp.315-320
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• 2013

Here, we show that radicicol, a fungal antibiotic, resulted in marked inhibition of inducible nitric oxide synthase (iNOS) transcription by the pancreatic beta cell line MIN6N8a in response to cytokine mixture (CM: TNF-${\alpha}$, IFN-${\gamma}$, and IL-$1{\beta}$). Treatment of MIN6N8a cells with radicicol inhibited CM-stimulated activation of NF-${\kappa}B$/Rel, which plays a critical role in iNOS transcription, in a dose-related manner. Nitrite production in the presence of PD98059, a specific inhibitor of the extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) pathway, was dramatically diminished, suggesting that the ERK1/2 pathway is involved in CM-induced iNOS expression. In contrast, SB203580, a specific inhibitor of p38, had no effect on nitrite generation. Collectively, this series of experiments indicates that radicicol inhibits iNOS gene expression by blocking ERK1/2 signaling. Due to the critical role that NO release plays in mediating destruction of pancreatic beta cells, the inhibitory effects of radicicol on iNOS expression suggest that radicicol may represent a useful anti-diabetic activity.

• 대한화장품학회지
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• 제28권1호
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• pp.71-79
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• 2002

In the aged skin especially in the face and eyelid, deep and slight wrinkles are one of the remarkable phenomena of aging and the cause of wrinkle is various. Among the cause of wrinkles an oxidative stress plays an important roles in wrinkle formation process. It caused the lipid peroxidation of cell membrane, the increase of the MMPs(MatrixMetalloProteinase) gene expression and cellular DNA damage. These ROS induced materials may cause the degradation of collagen matrix system in the dermis and cause the formation of skin wrinkle. So, it is very important for protecting skin wrinkle formation to regulate ROS activity. In this study, we developed one active ingredient having multi functional activities such as activation of collagen synthesis, inhibition of MMPs activity, lipid peroxidation and free radical scavenging activity and inhibition of free radical induced DNA damage in vitro. Pericarpium castaneae extracts showed collagen synthesis increase in Normal Human Fibroblast and the inhibition of elastase activity (IC$\_$50/ of Elastase: 43.9$\mu\textrm{g}$/㎖). It showed also anti-oxidative activity (IC$\_$50/ : 48$\mu\textrm{g}$/㎖) and free radical scavenging activity(IC$\_$50/: 7.6$\mu\textrm{g}$/㎖). Conclusively, Pericarpium castaneae extracts may be used as an ingredient for new anti-wrinkle cosmetics.

• Applied Biological Chemistry
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• 제46권1호
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• pp.32-38
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• 2003

시판되고 있는 두류 13종류의 70% 에탄을 추출물을 제조하여, 이들의 항산화 활성을 환원력, 지질과산화 억제 활성, superoxide radical 소저활성, hydroxyl radical 소거활성, mitomycin C로 유도된 DNA의 산화적 손상에 대한 억제활성을 지표로 조사하였다. 환원력은 예팥, 속피리, 유월콩 및 적두가 높았다. 지질과산화 억제능을 조사한 결과, linoleic acid 자동산화계를 이용한 실험계에서 모든 시료가 억제활성을 보인 반면, 토끼 적혈구막 지질과 산화에 대한 억제활성은 쥐눈이콩과 적두, 속피리에서만 관찰되었다. Superoxide radical 소거활성은 예팥, 나물콩, 적두, 쥐눈이콩에서 높게 나타났으며, hydroxyl radical 소거활성은 속피리, 청태, 예팥과 제비콩에서 높았다. Mitomycin C로 유도된 DNA의 산화적 손상에 대한 억제활성을 조사한 결과, 모든 품종들이 DNA의 산화적 손상을 억제할 수 있었으나, 특히 예팥, 쥐눈이콩, 나물콩, 녹두, 적두의 억제활성이 우수하였다. 이상의 실험결과에서 예팥, 적두, 쥐눈이콩, 속피리가 환원력, 지질과산화 억제, superoxide radical 및 hydroxyl radical 소거활성, DNA의 산화적 손상에 대한 억제활성 둥 항산화활성이 우수한 품종임을 알 수 있었다.