• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8271-8279
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• 2016

Background: Hepato-carcinogenesis is multifaceted in its molecular aspects. Among the interplaying agents are altered gap junctions, the proteasome/autophagy system, and mitochondria. The present experimental study was designed to outline the roles of these players and to investigate the tumor suppressive effects of curcumin with or without mesenchymal stem cells (MSCs) in hepatocellular carcinoma (HCC). Materials and Methods: Adult female albino rats were divided into normal controls and animals with HCC induced by diethyl-nitrosamine (DENA) and $CCl_4$. Additional groups treated after HCC induction were: Cur/HCC which received curcumin; MSCs/HCC which received MSCs; and Cur+MSCs/HCC which received both curcumin and MSCs. For all groups there were histopathological examination and assessment of gene expression of connexin43 (Cx43), ubiquitin ligase-E3 (UCP-3), the autophagy marker LC3 and coenzyme-Q10 (Mito.Q10) mRNA by real time, reverse transcription-polymerase chain reaction, along with measurement of LC3II/LC3I ratio for estimation of autophagosome formation in the rat liver tissue. In addition, the serum levels of ALT, AST and alpha fetoprotein (AFP), together with the proinflammatory cytokines $TNF{\alpha}$ and IL-6, were determined in all groups. Results: Histopathological examination of liver tissue from animals which received DENA-$CCl_4$ only revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules. Administration of curcumin, MSCs; each alone or combined into rats after induction of HCC improved the histopathological picture. This was accompanied by significant reduction in ${\alpha}$-fetoprotein together with proinflammatory cytokines and significant decrease of various liver enzymes, in addition to upregulation of Cx43, UCP-3, LC3 and Mito.Q10 mRNA. Conclusions: Improvement of Cx43 expression, nonapoptotic cell death and mitochondrial function can repress tumor growth in HCC. Administration of curcumin and/or MSCs have tumor suppressive effects as they can target these mechanisms. However, further research is still needed to verify their effectiveness.

• 한국수산과학회지
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• 제7권3호
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• pp.115-120
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• 1974

열처리 가공중의 발암성이 있는 nitrosamine의 전구물질이 되는 dimethylamine(DMA)의 함량 변화를 실험하였다. 신선한 어육중의 DMA함량은 명태가 피등어꼴두기, 조기. 고등어 보다 월등하게 많았다. 열처리 가공중의 DMA량의 변화를 보면 생시료에 비하여 명태는 열풍건조중 1.8배, 천일건조중 16,6배 증가하였다. 고등어는 배건중에 6.3배, 통조림 가공중에는 9.5배 DMA함량이 증가하였다. 한편 명태, 피등어꼴뚜기, 조기, 고등어 육에서는 dimethylamine, diethylamine은 검출되지 않았다.

• 한국연초학회지
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• 제29권2호
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• pp.59-65
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• 2007

The study was carried out to investigate water activity, physicochemical properties and color degree of burley tobacco stored in shelf with different moisture content for 56 days. The study was consist of two experimental designs, that is, moisture content in burley tobacco was kept to 13 to 15 %, 17 to 19 %, and 21 to 23 % under ambient temperature of $20^{\circ}C$ with relative humidity of 24 %, and another group of in burley tobacco was only kept in ambient temperature of $3^{\circ}C$ with relative humidity of 50 % for 56 days with same water content of former treatment. Normal leaves were kept for 56 days under 21 to 23% of moisture content with increased water activity and TSNA(tobacco-specific nitrosamine content. It was considered that favorable leaves conditions are due to favorable microbial growth resulting in increased TSNA content. The total nitrogen content has not changed in two experimental groups for 56 days, otherwise the nitrate form nitrogen and total alkaloid contents were only increased by 21 to 23 % of water content. Degree of pH change was slightly decreased in both storage and water treatment. It was more decreased in 21 to 23% of moisture content than that of other moisture content. In stored leaf tobacco, higher moisture content caused lower brightness, yellow degree, and carbonization quotient.

• 분석과학
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• 제28권1호
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• pp.1-7
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• 2015

4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco specific nitrosamine found only in tobacco products. The ability to monitor biomarker concentrations is very important in understanding environmental tobacco smoke (ETS). In this study, an efficient and sensitive method for the analysis of NNK in dust was developed and validated using liquid chromatography tandem mass spectrometry. Dust was collected with filter paper soaked in methanol. The standard solution and dust sample were diluted with 100 mM ammonium acetate and extracted using dichloromethane. Our calibration curves ranged from 25 to $10^4pg/mL$. Excellent linearity was obtained with correlation coefficient values between 0.9996 and 1.0000. The limit of detection (LOD) was 5 pg/mL ($S/N{\geq}3$) and the retention time was 10 min. The limit of quantification (LOQ) was 25 pg/mL, and the acceptance criteria was the rate of 98-103% (80-120% at levels up to $3{\times}LOQ$). The coefficient of variations (CV) was 2.8%. Accuracies determined from dust samples spiked with four different levels of NNK racurves ranged that from 25 to 104 pg/mL. Excellent linearity was obtained between 92.1% and 114%. The precision of the method was acceptable (5% of CV). The recovery rates of the whole analytical procedure at low, medium, and high levels were 105.7-116.5% for NNK. The carry-over effects during LC-MS/MS analysis were not observed for NNK. This manuscript summarizes the scientific evidence on the use of markers to measure ETS.

• Corrosion Science and Technology
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• 제16권1호
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• pp.31-37
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• 2017

A synergistic effect was observed in the combination of nitrite and ethanolamines. Ethanolamine is one of the representative organic corrosion inhibitors and can be categorized as adsorption type. However, nitrosamines can form when amines mix with sodium nitrite. Since nitrosamine is a carcinogen, the co-addition of nitrite and ethanolamine will be not practical, and thus, a non-toxic combination of inhibitors shall be needed. In order to maximize the effect of monoethanolamine, we focused on the addition of molybdate. Molybdate has been used to alternate the addition of chromate, but it showed insufficient oxidizing power relative to corrosion inhibitors. This work evaluated the synergistic effect of the co-addition of molybdate and monoethanolamine, and its corrosion mechanism was elucidated. A high concentration of molybdate or monoethanolamine was needed to inhibit the corrosion of ductile cast iron in tap water, but in the case of the co-addition of molybdate and monoethanolamine, a synergistic effect was observed. This synergistic effect could be attributed to the molybdate that partly oxidizes the metallic surface and the monoethanolamine that is simultaneously adsorbed on the graphite surface. This adsorbed layer then acts as the barrier layer that mitigates galvanic corrosion between the graphite and the matrix.

• 한국식품영양과학회지
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• 제30권4호
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• pp.589-593
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• 2001

폐자원으로 얻어지는 게껍질, 감귤껍질, 참깨박이 free radical 반응 및 지방산화 억제에 미치는 영향과 nitrosamine 생성의 직접적인 영향인자인 아질산염에 대한 폐자원의 분해 효과를 검토하였다. 폐자원(게껍질, 참깨박, 감귤껍질)으로 부터 유효성분인 chitosan, crude sesamol, ascorbic acid는 각각 11.6%, 2.2%, 2.8%로 나타났으며, TBARS값은 대조구에 비하여 낮은 값을 나타내어 항산화성이 인정되었다. 또한, 전자공여능은 chitosan 29.8%, crude sesamol 35.2%, 감귤껍질 추출물 15.8%로 나타났으며, SOD 유사활성능은 전반적으로 SOD 유사활성이 8% 이상으로 나타났으며, chitosan 51.3%, crude sesamol 19.9%, 감귤껍질 추출물 8.4%로 나타났다. 폐자원 추출물의 nitrite 소거작용은 pH 1.2에서 chitosan 17.4%, crude sesamol 56.4%, 감귤껍질 추출물 19.0%로 나타났으며, crude sesamol이 pH 1.2와 pH 3.0에서 각각 56.4%, 55.4%의 높은 소거작용을 나타내었다.

• 한국식품영양과학회지
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• 제23권1호
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• pp.137-142
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• 1994

Glucose-아미노산(Lys, Gly, His, Arg)모델계 반응을 통해 생성된 Maillard반응생성물과 비투석성 melanoidin의 NDMA생성억제능에 대한 영향을 검토하였는데 그 결과를 요약하면 다음과 같다. 1. Maillard반응생성물과 비투석성 melanoidin의 모든 시료에서 NDMA생성억제능이 나타났으며, 환원능을 소멸시키고 난 후의 NDMA생성억제능은 환원능이 소실되기 이전보다 1/2이하로 감소하여 이들 시료에 존재하는 환원능이 NDMA생성억제에 있어서 주요 인자로 나타났다. 2. Melanoidin과 ascorbic acid를 동량 첨가하였을 때, NDMA생성억제능은 ascorbic acid를 동량 첨가하였을 때, NDMA생성억제능은 ascorbic acid와 비슷한 경향을 나타내어 비투석성 melanoidin의 NDMA생성억제능이 우수한 것으로 나타났다. 3. Maillard반응생성물에 의한 NDMA생성억제작용은 Maillard반응생성물에 존재하는 비투석성 melanoidin이 크게 관여하고 이들 억제작용에는 Maillard반응생성물의 환원능이 크게 관여 하는 것으로 나타났다.

• Plant Resources
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• 제2권1호
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• pp.26-30
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• 1999

Nitrate in edible vegetables is converted to nitrite by nitrate reductase(NR) and/or bacteria in intestines. Nitrite and amino, in the intestine of some animals and human, bind to form nitrosamine, which is toxic and known as carcinogen. This study was carried out to examine the effect of added chlorides and their concentrations on growth, yield and nitrate content in leaf lettuce plants in hydroponics. Seeds of lettuce cv, "Samsunjokchukmyon" were planted on April 29, and seedlings were planted on June 2, and were cultured until July 5 in 1998. KCI and CaCl₂ were used as chloride source and their concentrations were 1, 2 and 4 me/L, respectively, in the lettuce standard nutrient solution for National Horticultural Research Institute(NHRI). Completely randomized design with 3 replications was used. Nitrate content and NR activity were measured 2 and 5 weeks after planting(WAP). The obtained results were summarized as the follows : Leaf weight per plant was difference from harvest dates and treatments, but total leaf weight was not significantly different among treatments. Number of leaves was higher in KCI 2 me/L, CaCl₂1 me/L and control at 2 WAP than the others, and was higher in KCI 1 me/L, and control at 3 WAP than others, and was higher in control at 5 WAP. Total number of harvested leaves was the highest in control with 14, which followed by KCI 2 me/L and CaCl₂1 me/L. Nitrate content was decreased by addition of chloride in nutrient solution. Nitrate content in the 3rd and 9th leaves was significantly decreased. NR activity was higher in control and CaCl₂ addition treatments, while KCI addition treatments reduced NR activity. However, no direct relationship with nitrate was observed. Growth characteristics such leaf length and leaf width were not significantly influenced by chloride addition.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4597-4606
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• 2012

Cholangiocarcinoma (CCA) is an uncommon adenocarcinoma which arises from the epithelial cells of the bile ducts. The aim of the study was to investigate the cytotoxicity, toxicity, and anticancer activity of a crude ethanolic extract of ginger (Zingiber officinale Roscoe) against CCA. Cytotoxic activity against a CCA cell line (CL-6) was assessed by calcein-AM and Hoechst 33342 assays and anti-oxidant activity was evaluated using the DPPH assay. Investigation of apoptotic activity was performed by DNA fragmentation assay and induction of genes that may be involved in the resistance of CCA to anticancer drugs (MDR1, MRP1, MRP2, and MRP3) was examined by real-time PCR. To investigate anti-CCA activity in vivo, a total of 80 OV and nitrosamine (OV/DMN)-induced CCA hamsters were fed with the ginger extract at doses of 1000, 3000, and 5000 mg/kg body weight daily or every alternate day for 30 days. Control groups consisting of 10 hamsters for each group were fed with 5-fluorouracil (positive control) or distilled water (untreated control). Median $IC_{50}$ (concentration that inhibits cell growth by 50%) values for cytotoxicity and anti-oxidant activities of the crude ethanolic extract of ginger were 10.95, 53.15, and $27.86{\mu}g/ml$, respectively. More than ten DNA fragments were visualized and up to 7-9 fold up-regulation of MDR1 and MRP3 genes was observed following exposure to the ethanolic extract of ginger. Acute and subacute toxicity tests indicated absence of any significant toxicity at the maximum dose of 5,000 mg/kg body weight given by intragastric gavage. The survival time and survival rate of the CCA-bearing hamsters were significantly prolonged compared to the control group (median of 54 vs 17 weeks). Results from these in vitro and in vivo studies thus indicate promising anticancer activity of the crude ethanolic extract of ginger against CCA with the absence of any significant toxicity. Moreover, MDR1 and MRP3 may be involved in conferring resistance of CCA to the ginger extract.

• Toxicological Research
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• 제23권1호
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• pp.55-63
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• 2007

Diethylnitrosamine (DEN) is a nitrosamine compound that can induce a variety of liver lesions including hepatic carcinoma, forming DNA-carcinogen adducts. In the present study, microarray analyses were performed with Affymetrix Murine Genome 430A Array in order to identify the gene-expression profiles for DEN and to provide valuable information for the evaluation of potential hepatotoxicity. C57BL/6NCrj mice were orally administered once with DEN at doses of 0, 3, 7 and 20 mg/kg. Liver from each animal was removed 2, 4, 8 and 24 hrs after the administration. The histopathological analysis and serum biochemical analysis showed no significant difference in DEN-treated groups compared to control group. Conversely, the principal component analysis (PCA) profiles demonstrated that a specific normal gene expression profile in control groups differed clearly from the expression profiles of DEN-treated groups. Within groups, a little variance was found between individuals. Student's t-test on the results obtained from triplicate hybridizations was performed to identify those genes with statistically significant changes in the expression. Statistical analysis revealed that 11 genes were significantly downregulated and 28 genes were upregulated in all three animals after 2 h treatment at 20 mg/kg. The upregulated group included genes encoding Gdf15, JunD1, and Mdm2, while the genes including Sox6, Shmt2, and SIc6a6 were largely down regulated. Hierarchical clustering of gene expression also allowed the identification of functionally related clusters that encode proteins related to metabolism, and MAPK signaling pathway. Taken together, this study suggests that match with a toxicant signature can assign a putative mechanism of action to the test compound if is established a database containing response patterns to various toxic compounds.