• Korean Journal of Veterinary Pathology
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• v.5 no.1
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• pp.23-28
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• 2001

This study was conducted to assess the chemopreventive effects of sodium selenite in the rat medium-term multi-organ bioassay using a DMBDD model (DEN+MNU+BBN+DMH+DHPN). Seventy five,6-week-old, male SD rats were divided into 3 groups. The animals in group 1 received DEN(diethylnitrosamine,100 mg/kg bw, single i.p., in saline), MNU (N-methyl-nitrosourea,20 mg/kg bw, i.p.,4 times for 2 weeks), BBN (N-butyl-N-(4-hydroxybutyl) nitrosamine, 0.2% in drinking water for 2 weeks), DMH (1,2-dimethylhydrazine, 40 mg/kg bw, s.c., in saline.4 times (or 2 weeds), and DHPN (N-bis(2-hydroxy-pro-pal)nitrosamine,0.1% in drinking water for 2 weeks), then were placed on sodium selenite (4 ppm in drinking water) for 22 weeks from weeks 4 to 26. The animals in group 2 were given DMBDD alone. The animals in group 3 were given sodium selenite alone. Animals were sacrificed at week 12 for ACF quantitative analysis and at week 26 for tumor induction. The body weights in the group 1 were significantly decreased compared with those of group 2. The tumor multiplicities of large intestine in the group 1 were significantly decreased compared with those of group 2 (P<0.05). These results indicate that sodium selenite may have a potential as chemopreventive agents of colon carcinogenesis.

• Biomolecules & Therapeutics
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• v.3 no.2
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• pp.122-131
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• 1995

Five human cancer cell lines (HeLa S3, Hep 3B, KATO III, Hs 683, HeLa MR) and one human normal cell line (WI-38) were examined cell viability, northern blot analysis, western blot analysis, and in situ hybridization for the expression $O_{6}$ -methylguanine-DNAmethyltransferase (MGMT), which can repair $O_{6}$ -methylguanine produced in DNA by alkylating agents. In cell viability test, the lethal sensitivities of each strain against anti-tumor drug N,N-bis(2-chloroethyl)- N-nitrosourea (BCNU) were counted, and both BCNU treated and untreated cell extracts were examined for their MGMT inducibility by RNA dot blot analysis. Cell lines did not show MGMT induction by BCNU pretreatment. Tlle MGMT activity was assayed by measuring the $^3$H radioactivity transferred from the substrate DNA containing [methyl-$^3$H)-O$_{6}$ -methylguanine to acceptor molecules in the cell extracts. Extracts from the majority of tumor strains and normal cells contained substantial MGMT activity of varying degree, while the known Mer$^{[-10]}$ cell (lacked or severely depleted in MGMT activity) Hela MR, and Hs 683 (proved to be Mer$^{[-10]}$ ) were much more sensitive to BCNU than the rest of tumor strains, as measured by cell viability test. Overall results above, KATO III showed the highest expression level of MGMT among the strains examined. Furthermore, with all the tumor and normal strains tested, a good correlation was observed between MGMT expression and cellular resistance to BCNU. The varying levels of expression of MGMT in human cancer cells found in this study should provide a molecular basis for MGMT expression among tumor strains from different tissue origin, the information of antitumor agents selection for chemotherapy of cancers.

• Nutrition Research and Practice
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• v.14 no.3
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• pp.203-217
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• 2020

BACKGROUND/OBJECTIVE: Centella asiatica, also known as Gotu kola, is a tropical medicinal plant native to Madagascar, Southeast Asia, and South Africa. It is well known to have biological activities, including wound healing, anti-inflammatory, antidiabetic, cytotoxic, and antioxidant effects. The purpose of this study was to determine the efficacy of extracts of C. asiatica against age-related eye degeneration and to examine their physiological activities. MATERIALS/METHODS: To determine the effects of CA-HE50 (C. asiatica 50% EtOH extract) on retinal pigment cells, we assessed the cytotoxicity of CoCl₂ and oxidized-A2E in ARPE-19 cells and observed the protective effects of CA-HE50 against N-methyl-N-nitrosourea (MNU)-induced retinal damage in C57BL/6 mice. In particular, we measured factors related to apoptosis and anti-oxidation and the protein levels of rhodopsin/opsin. We also measured glucose uptake to characterize glucose metabolism, a major factor in cell protection. RESULTS: Induction of cytotoxicity with CoCl₂ and oxidized-A2E inhibited decreases in the viability of ARPE-19 cells when CA-HE50 was administered, and promoted glucose uptake under normal conditions (P < 0.05). In addition, CA-HE50 inhibited degeneration/apoptosis of the retina in the context of MNU-induced toxicity (P < 0.05). In particular, CA-HE50 at 200 mg/kg inhibited the cleavage of pro-caspase-3 and pro-poly (ADP-ribose)-polymerase and maintained the expressions of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 similar to normal control levels. Rhodopsin/opsin expression was maintained at a higher level than in normal controls. CONCLUSION: A series of experiments confirmed that CA-HE50 was effective for inhibiting or preventing age-related eye damage/degeneration. Based on these results, we believe it is worthwhile to develop drugs or functional foods related to age-related eye degeneration using CA-HE50.

• Korean Journal of Veterinary Research
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• v.54 no.3
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• pp.171-177
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• 2014

Garlic and mugwort have long been used in traditional medicine to prevent various diseases. Several in vitro studies have reported protective efficacies of garlic and mugwort in cases of gastric cancer. In the present study, we investigated the cancer preventive effects of garlic and mugwort mixture extract (GME) in a Helicobacter (H.) pylori-associated gastric carcinogenesis mouse model. To induce gastric cancer, C57BL/6 mice were treated with N-methyl-N-nitrosourea and H. pylori. Various concentrations of GME (0, 100, 500, and 1,000 ppm) were then fed to the mice for 38 weeks, after which the tumor tissues were examined for histopathology, mucin histochemistry and ${\beta}$-catenin. The incidence of gastric tumors was significantly lower in the highest dose GME-treated mice (46.7%) than control mice (85.7%) (p < 0.05). The multiplicity and size of tumors were also significantly reduced by GME feeding in a dose-dependent manner (p < 0.01). Furthermore, GME suppressed the H. pylori-associated chronic inflammation measured by histologic grading of H. pylori density, chronic gastritis, glandular atrophy and intestinal metaplasia in non-tumorous gastric mucosae. Our data suggest that GME suppresses gastric tumorigenesis via suppression of H. pylori-associated chronic inflammation.

• Korean Journal of Plant Tissue Culture
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• v.27 no.2
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• pp.89-94
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• 2000

In order to induce the mutants of Gentiana axillariflora Leveille, nodes were cultured on Schenk and Hilderbrandt (SH) medium containing TDZ 2 mg/L, BAP 2mg/L, GA3 0.5 mg/L and 0.1 mg/L NAA and each mutagen of ethylmethanesulfate (EMS), colchicine, N-methyl-N-nitrosourea (MNU), and sodium azide (NaN$_3$) through filtration. Comparision of morphological characteristics and survival rate in each mutant plants differed depending on mutagen sources and their concentrations. When EMS were treated on nodes, the regenerated plants was thin and albino, regenerated shoots appeared 'erectoides type' and get twisted. The case of colchicine were treated on nodes, the survival rate was from 84% to 97% at ail concentration after 30days but the rate of survival was decreased about 50% at 200 $\mu$M after 60days. The treatment of NaN$_3$200 $\mu$M was not survived. The survival rate was extremely decreased in MNU treatment at 500$\mu$M, according to concentrations two types of leaf characteristic were obtained. Type I of leaf characteristic was modified from oblanceolate to oboid at leaf shape and type II of leaf characteristic was modified from light green to dark violet at leaf color. RAPD analysis was carried out to check the genetic modification of regenerated plants by mutagen treatments. Three polymorphic DNA fragments out of thirty-seven obtained by RAPDs were observed in regenerated plants using 5 decamer primers.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.3939-3944
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• 2014

Background: To elucidate the role of rapamycin and PF4 on apoptosis regulation via Bax (pro-apoptosis), Bcl-2 (anti-apoptosis) and survivin activation on the growth in the 1-methyl-1-nitrosourea-induced invasive breast carcinoma model. Materials and Methods: Thirty five female Sprague Dawley rats at age 21-day old were divided into 4 groups; Group 1 (control, n=10), Group 2 (PF4, n=5), Group 3 (rapamycin, n=10) and Group 4 (rapamycin+PF4, n=10). MNU was administered intraperitionally, dosed at 70mg/kg body weight. The rats were treated when the tumors reached the size of $14.5{\pm}0.5mm$ and subsequently sacrificed after 5 days. Rapamycin and PF4 were administered as focal intralesional injections at the dose of $20{\mu}g$/lesion. The tumor tissue was then subjected to histopathological examinations for morphological appraisal and immunohistochemical assessment of the pro-apoptotic marker, Bax and anti-apoptotic markers, Bcl-2 and survivin. Results: The histopathological pattern of the untreated control cohort showed that the severity of the malignancy augments with mammary tumor growth. Tumors developing in untreated groups were more aggressive whilst those in treated groups demonstrated a transformation to a less aggressive subtype. Combined treatment resulted in a significant reduction of tumor size without phenotypic changes. Bax, the pro-apoptotic marker, was significantly expressed at higher levels in the rapamycin-treated and rapamycin+PF4-treated groups compared to controls (p<0.05). Consequently, survivin was also significantly downregulated in the rapamycin-treated and rapamycin+PF4-treated group and this was significantly different when compared to controls (p). Conclusions: In our rat model, it could be clearly shown that rapamycin specifically affects Bax and survivin signaling pathways in activation of apoptosis. We conclude that rapamycin plays a critical role in the induction of apoptosis in MNU-induced mammary carcinoma.

• Journal of Microbiology and Biotechnology
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• v.28 no.4
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• pp.645-651
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• 2018

The carcinogenicity of chemicals in the environment is a major concern. Recently, numerous studies have attempted to develop methods for predicting carcinogenicity, including rodent and cell-based approaches. However, rodent carcinogenicity tests for evaluating the carcinogenic potential of a chemical to humans are time-consuming and costly. This study focused on the development of an alternative method for predicting carcinogenicity using quantitative PCR (qPCR) and colon cancer stem cells. A toxicogenomic method, mRNA profiling, is useful for predicting carcinogenicity. Using microarray analysis, we optimized 16 predictive gene sets from five carcinogens (azoxymethane, 3,2'-dimethyl-4-aminobiphenyl, N-ethyl-n-nitrosourea, metronidazole, 4-(n-methyl-n-nitrosamino)-1-(3-pyridyl)-1-butanone) used to treat colon cancer stem cell samples. The 16 genes were evaluated by qPCR using 23 positive and negative carcinogens in colon cancer stem cells. Among them, six genes could differentiate between positive and negative carcinogens with a p-value of ${\leq}0.05$. Our qPCR-based prediction system for colon carcinogenesis using colon cancer stem cells is cost- and time-efficient. Thus, this qPCR-based prediction system is an alternative to in vivo carcinogenicity screening assays.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.9
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• pp.1313-1319
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• 2010

Rice cultivars of Goami2 (G2), Baegjinju (BJJ), and Sulgaeng (SG) with different amylose contents were developed by mutation breeding via N-methyl-N-nitrosourea (MNU) treatment to Ilpumbyeo (IP), high japonica rice. They were identified by different appearances such as grain size, color, and shape. In this experiment, the compositional and physical qualities of those cultivars were examined. The G2 rice classified as a high-amylose rice cultivar was significantly higher in its non-digestable carbohydrates contents. Linoleic and oleic acid were composed of 70~75% of all fatty acids composition regardless of milled and brown rice, except G2 rice in which palmitic acid was the major fatty acid followed by linoleic acid and oleic acid in order. Major amino acids were aspartic acid, glutamic acid, and hydroxy lysine. It was found that cysteine contents were higher in the cultivars of endosperm mutant rice. The DSC analysis revealed that enthalpy was the highest in BJJ followed by SG, IP, and G2 rice. The lowest enthalpy of G2 might be attributable to the higher amylose content. Ilpumbyeo in its cooked rice form showed the highest in Toyo value and less in hardness, but G2 was vise versa. Results of gelatinization and cooked rice properties suggest that G2 was less suitable for cooked rice, but has a potential for functional ingredients from nutritional point of view. The BJJ and SG could be used for traditional cooking as well as for processed foods.

• Korean Journal of Food Science and Technology
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• v.51 no.2
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• pp.109-113
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• 2019

The soft rice varieties, Hangaru and Singil, were developed via mutation breeding using N-methyl-N-nitrosourea treatment to obtain dry-milled rice flours. The physicochemical, morphological, and pasting properties of these starches were compared with those of Seolgaeng and Chuchung starches. Singil starch was found to exhibit the highest amylose content and initial pasting temperature, whereas Hangaru starch exhibited the highest water binding capacity and swelling power. Hangaru starch's granule size at $d_{50}$ was the largest among the four different starch types. Some Seolgaeng, Hangaru, and Singil granules were observed to have a round-faced polygon shape. Furthermore, the crystallinity of all four starch types was type A. The peak, trough, and final viscosities of the soft rice starches were also lower than those of normal starches. Notably, Hangaru starch showed the highest breakdown viscosity, but the lowest total setback viscosity among the four starches. From these results, the starch characteristics of the soft rice flours were discovered to be different based on the rice variety.

• Korean Journal of Breeding Science
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• v.43 no.6
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• pp.532-537
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• 2011

'Seolgaeng' is a new Japonica rice variety developed from an 'Ilpumbyeo' mutant line, N-methyl-N-nitrosourea (MNU) treatment on fertilized egg cell, by a rice breeding team of National Crop Experiment Station, Rural Development Administration in 2001. This variety has about 134 days of growth duration from transplanting to harvesting in central plain area of Korea, a good semi-elect plant type and resistant to lodging with strong culm. The number of panicles/hill of 'Seolgaeng' is more than that of 'Hwaseongbyeo'. The milled rice appearance of this cultivar is an opaque, but it has amylose content (19.3%) similar to 'Hwaseongbyeo'. It is superior to hypae formation of Aspergillus orzyae in the making of fermented rice and amount of pigmentation in fermented rice by Monascus anka that of 'Ilpumbyeo'. This variety showed slow leaf senescence and considerable resistance to viviparous germination. It is moderately resistant to leaf blast and susceptible to bacterial blight, virus disease and insect pests. The yield performance of this rice cultivar is about 5.27 MT/ha in milled rice in local adaptability test for three years from 1999 to 2001). 'Seolgaeng' is adaptable to central and southern plain areas of Korea.