• Title/Summary/Keyword: Nitrosourea

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Rapamycin and PF4 Induce Apoptosis by Upregulating Bax and Down-Regulating Survivin in MNU-Induced Breast Cancer

  • Al-Astani Tengku Din, Tengku Ahmad Damitri;Shamsuddin, Shazana Hilda;Idris, Fauziah Mohamad;Wan Mansor, Wan Nor Ariffin;Abdul Jalal, Muhammad Irfan;Jaafar, Hasnan
    • 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.

Physicochemical Properties of Rice Cultivars with Different Amylose Contents (아밀로스 함량이 다른 쌀 품종의 이화학적 특성)

  • Choi, In-Duck
    • 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.

Alternative Carcinogenicity Screening Assay Using Colon Cancer Stem Cells: A Quantitative PCR (qPCR)-Based Prediction System for Colon Carcinogenesis

  • Bak, Yesol;Jang, Hui-Joo;Shin, Jong-Woon;Kim, Soo-Jin;Chun, Hyun woo;Seo, Ji-Hye;No, Su-Hyun;Chae, Jung-il;Son, Dong Hee;Lee, Seung Yeoun;Hong, Jintae;Yoon, Do-Young
    • 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.

Induction and RAPD Analysis of Mutant Plants by Chemical Mutagens in Gentiana axillariflora Leveille (큰용담 (Gentiana axillarifloa L,) 기내배양에서 화학돌연변이원 처리에 의한 돌연변이주 유기 및 RAPD 분석)

  • 임정대;김명조;유창연
    • 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.

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Characteristics of BCNU-loaded PLGA Wafers (BCNU를 함유한 생분해성 PLGA 웨이퍼의 특성분석)

  • 안태군;강희정;이진수;성하수;정제교
    • Polymer(Korea)
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    • v.26 no.5
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    • pp.691-700
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    • 2002
  • Interstitial therapy using biodegradable polymeric device loaded with anticancer agent can deliver the drug to the tumor site at high concentration, resulting in an increase of therapeutic efficacy. 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU, carmustine) is most commonly used as chemotherapeutic agent for brain tumors. The design of implantable device is regarded as an important factor lot the efficient delivery of antitumor agent to targeting site. In order to control the release profile of drug, the release pattern of BCNU with the changes of various dimension and additives was investigated. The PLGA wafers containing 3.85, 10, 20 and 30% of BCNU were prepared in various shape (diameter of 3, 5 and 10 mm, thickness of 0.5, 1 and 2 mm) by direct compression method. In vitro drug release profile of BCNU-loaded PLGA wafers could be controlled by changing the dimension of wafers such as initial drug content, weight, diameter, thickness, volume and surface area of wafers, as well as PLGA molecular weight and additives. Drug release from BCNU-loaded PLGA wafers was facilitated with an increase of BCNU-loading amount or presence of poly(N-vinylpyrrolidone)(PVP) or sodium chloride (NaCl). The effects of various geometric factors and additives on the BCNU release pattern were confirmed by the investigation of mass loss and morphology of BCNU-loaded PLGA wafers.

Physicochemical and pasting properties of rice starches from soft rice varieties developed by endosperm mutation breeding (배유 돌연변이처리로 개발된 연질미 전분의 이화학적 특성)

  • Kim, Jae Suk;No, Junhee;Shin, Malshick
    • 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.

A Lodging Tolerant, Opaque Rice Cultivar 'Seolgaeng' (벼 내도복 뽀얀멥쌀 신품종 '설갱')

  • Hong, Ha-Cheol;Moon, Huhn-Pal;Choi, Hae-Chune;Hwang, Hung-Goo;Kim, Yeon-Gyu;Kim, Hong-Yeol;Yea, Jong-Doo;Shin, Young-Seop;Kang, Kyung-Ho;Choi, Yong-Hwan;Cho, Young-Chan;Baek, Man-Kee;Yang, Chang-Ihn;Choi, Im-Soo;Ahn, Sang-Nag;Yang, Sae-June
    • 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.

A New Mid-late Maturing Rice Variety, 'Honong' with High-Quality and Multiple Disease Resistance (중만생 고품질 복합내병성 벼 신품종 '호농')

  • Kim, Ki-Young;Shin, Mun-Sik;Ko, Jae-Kwon;Nam, Jeong-Kwon;Ha, Ki-Yong;Baek, Man-Gee;Ko, Jong-Cheol;Kim, Bo-Kyeong;Park, Hyun-Su;Shin, Woon-Chul;Kang, Hyun-Jung;Choung, Jin-Il;Kim, Woo-Jae;Mo, Young-Jun;Kim, Jung-Gon
    • Korean Journal of Breeding Science
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    • v.42 no.3
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    • pp.252-256
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    • 2010
  • 'Honong' is a new japonica rice variety developed and registered by the rice breeding team of Department of Rice and Winter Cereal Crop, NICS, RDA in 2009. This variety was derived from mutagen MNU (N-methyl-N-nitrosourea) treatment on fertilized egg cells of Unbong31. This variety has about 126 days growth duration from transplanting to harvesting in west-southern coast, Honam and Youngnam plain of Korea. It has 79 cm in culm length and is tolerant to lodging. In reaction to biotic and abiotic stresses, it show resistance to blast, bacterial blight pathogen races from $K_1$ to $K_3$ and stripe virus, but susceptible to other major diseases and insect pests. The milled rice of 'Honong' exhibits translucent, relatively clear non-glutinous endosperm and medium short grain. It has higher amylose content (20.3%) and lower protein content (6.3%), and good palatability of cooked rice compared with Nampyeong. The milled rice yield performance of this variety is about 5.44MT/ha in local adaptability test for three years. 'Honong' would be adaptable to west-southern coast, Honam and Youngnam plain of Korea.