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https://www.readbyqxmd.com/read/28074112/isolation-and-characterization-of-antimutagenic-components-of-glycyrrhiza-aspera-against-n-methyl-n-nitrosourea
#1
Keiko Inami, Yusuke Mine, Jin Tatsuzaki, Chihiro Mori, Masataka Mochizuki
BACKGROUND: A powdered ethanolic extract of Glycyrrhiza aspera root exhibits antimutagenic activity against N-methyl-N-nitrosourea (MNU) based on the Ames assay with Salmonella typhimurium TA1535. The aim of this study was to identify the antimutagenic components of the powdered ethanolic extract of G. aspera root. RESULTS: The powdered ethanolic extract of G. aspera root was sequentially suspended in n-hexane, carbon tetrachloride, dichloromethane, ethyl acetate, and ethanol, and each solvent soluble fraction and the residue were assayed for antimutagenic activity against MNU in S...
2017: Genes and Environment: the Official Journal of the Japanese Environmental Mutagen Society
https://www.readbyqxmd.com/read/28069436/streptozotocin-causes-neurotoxic-effect-in-cultured-cerebellar-granule-neurons
#2
Elisaveta E Genrikhs, Elena V Stelmashook, Sergey A Golyshev, Olga P Aleksandrova, Nickolay K Isaev
Streptozotocin (STZ) is a glucosamine-nitrosourea compound used for experimental simulation of sporadic Alzheimer's disease at intracerebroventricular administration in vivo. The studies of STZ influence on neurons of central nervous system performed on the primary cultures are practically absent. We have shown the application of STZ (1-5mM) in primary culture for 48h induced strong dose-dependent death in cultured cerebellar granule neurons. This toxic effect was decreased by pyruvate, insulin partially. Using the indicator Fluo-4 AM for measurements of intracellular calcium ions and tetramethylrhodamine ethyl ester (TMRE) for detection of changes of mitochondrial membrane potential in live cells we have shown that 5 h-exposure to STZ induced intensive increase of Fluo-4 and decrease TMRE fluorescence in neurons...
January 6, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28057804/cell-cycle-progression-dictates-the-requirement-for-bcl2-in-natural-killer-cell-survival
#3
Charlotte Viant, Sophie Guia, Robert J Hennessy, Jai Rautela, Kim Pham, Claire Bernat, Wilford Goh, Yuhao Jiao, Rebecca Delconte, Michael Roger, Vanina Simon, Fernando Souza-Fonseca-Guimaraes, Stephanie Grabow, Gabrielle T Belz, Benjamin T Kile, Andreas Strasser, Daniel Gray, Phillip D Hodgkin, Bruce Beutler, Eric Vivier, Sophie Ugolini, Nicholas D Huntington
Natural killer (NK) cells are innate lymphoid cells with antitumor functions. Using an N-ethyl-N-nitrosourea (ENU)-induced mutagenesis screen in mice, we identified a strain with an NK cell deficiency caused by a hypomorphic mutation in the Bcl2 (B cell lymphoma 2) gene. Analysis of these mice and the conditional deletion of Bcl2 in NK cells revealed a nonredundant intrinsic requirement for BCL2 in NK cell survival. In these mice, NK cells in cycle were protected against apoptosis, and NK cell counts were restored in inflammatory conditions, suggesting a redundant role for BCL2 in proliferating NK cells...
January 5, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28049248/nestin-expression-in-the-adult-mouse-retina-with-pharmaceutically-induced-retinal-degeneration
#4
Chan Hee Moon, Heeyoon Cho, Yoon Kyung Kim, Tae Kwann Park
The present study investigated the temporal pattern and cellular localization of nestin in the adult mouse retina with pharmaceutically induced retinal degeneration using N-methyl-N-nitrosourea (MNU). After a single intraperitoneal injection of MNU in 8-week-old C57BL/6 mice, the animals were sacrificed at 1, 3, 5, 7, and 21 days (n = 6, in each stage). The eyes were examined by means of immunohistochemical tests using nestin, ionized calcium-binding adaptor molecule (Iba-1), CD11b, F4/80, and glial fibrillary acidic protein (GFAP)...
February 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28040797/disease-subtype-independent-biomarkers-of-breast-cancer-chemoprevention-by-the-ayurvedic-medicine-phytochemical-withaferin-a
#5
Suman K Samanta, Anuradha Sehrawat, Su-Hyeong Kim, Eun-Ryeong Hahm, Yongli Shuai, Ruchi Roy, Subrata K Pore, Krishna B Singh, Susan M Christner, Jan H Beumer, Nancy E Davidson, Shivendra V Singh
BACKGROUND: A nontoxic chemopreventive intervention efficacious against different subtypes of breast cancer is still a clinically unmet need. The present study was undertaken to determine the efficacy of an Ayurvedic medicine phytochemical (Withaferin A, [WA]) for chemoprevention of breast cancer and to elucidate its mode of action. METHODS: Chemopreventive efficacy of WA (4 and 8 mg/kg body weight) was determined using a rat model of breast cancer induced by N-methyl-N-nitrosourea (MNU; n = 14 for control group, n = 15 for 4 mg/kg group, and n = 18 for 8 mg/kg group)...
June 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28040063/pivotal-role-of-glutathione-depletion-in-enos-uncoupling-of-lps-treated-huvecs
#6
L Chen, E Liu, D Cao, S Li, C Xiao, M Xiong, Q Kou
The present study investigated the relationship between uncoupling of endothelial nitric oxide synthase (eNOS) and vascular endothelial cell (VEC) oxidative stress (OS) during sepsis and the role of eNOS glutathionylation in eNOS uncoupling of septic VECs. Human umbilical vein endothelial cells (HUVECs) cultured in vitro (EA.hy269 cell line) were incubated with Dulbecco's modified Eagle's medium (DMEM) (normal control group), lipopolysaccharide (LPS) (sepsis group), 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (glutathionylation group), and LPS+ dithiothreitol (DTT) (deglutathionylation sepsis group)...
November 30, 2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/27994066/phase-iii-randomized-study-of-radiation-and-temozolomide-versus-radiation-and-nitrosourea-therapy-for-anaplastic-astrocytoma-results-of-nrg-oncology-rtog-9813
#7
Susan Chang, Peixin Zhang, J Gregory Cairncross, Mark R Gilbert, Jean-Paul Bahary, Carol A Dolinskas, Arnab Chakravarti, Kenneth D Aldape, Erica H Bell, David Schiff, Kurt Jaeckle, Paul D Brown, Geoffrey R Barger, Maria Werner-Wasik, Helen Shih, David Brachman, Marta Penas-Prado, H Ian Robins, Karl Belanger, Christopher Schultz, Grant Hunter, Minesh Mehta
BACKGROUND: The primary objective of this study was to compare the overall survival (OS) of patients with anaplastic astrocytoma (AA) treated with radiotherapy (RT) and either temozolomide (TMZ) or a nitrosourea (NU). Secondary endpoints were time to tumor progression (TTP), toxicity, and the effect of IDH1 mutation status on clinical outcome. METHODS: Eligible patients with centrally reviewed, histologically confirmed, newly diagnosed AA were randomized to receive either RT+TMZ (n = 97) or RT+NU (n = 99)...
December 18, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/27965370/genetic-characterization-of-a-mouse-line-with-primary-aldosteronism
#8
Luis Gustavo Perez-Rivas, Yara Rhayem, Sibylle Sabrautzki, Constanze Hantel, Birgit Rathkolb, Martin Hrabé de Angelis, Martin Reincke, Felix Beuschlein, Ariadni Spyroglou
In an attempt to define novel genetic loci involved in the pathophysiology of primary aldosteronism a mutagenesis screen following treatment with the alkylating agent N-ethyl-N-nitrosourea was established for the parameter aldosterone. One of the generated mouse lines with hyperaldosteronism was phenotypically and genetically characterized. This mouse line had high aldosterone levels but normal creatinine and urea values. The steroidogenic enzyme expression levels in the adrenal gland did not differ significantly among phenotypically affected and unaffected mice...
December 13, 2016: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/27959934/mice-with-an-n-ethyl-n-nitrosourea-enu-induced-tyr209asn-mutation-in-natriuretic-peptide-receptor-3-npr3-provide-a-model-for-kyphosis-associated-with-activation-of-the-mapk-signaling-pathway
#9
Christopher T Esapa, Sian E Piret, M Andrew Nesbit, Nellie Y Loh, Gethin Thomas, Peter I Croucher, Matthew A Brown, Steve D M Brown, Roger D Cox, Rajesh V Thakker
Non-syndromic kyphosis is a common disorder that is associated with significant morbidity and has a strong genetic involvement; however, the causative genes remain to be identified, as such studies are hampered by genetic heterogeneity, small families and various modes of inheritance. To overcome these limitations, we investigated 12 week old progeny of mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU) using phenotypic assessments including dysmorphology, radiography, and dual-energy X-ray absorptiometry...
2016: PloS One
https://www.readbyqxmd.com/read/27931818/evaluation-of-the-pigret-assay-as-a-short-term-test-using-a-single-dose-of-diethylnitrosamine
#10
Kunio Wada, Risako Nishino, Tomoki Fukuyama, Kyomu Matsumoto
The PIGRET assay, which was developed as the Pig-a assay in reticulocytes, can detect mutagenicity of compounds earlier than the Pig-a assay in total red blood cells (RBC; RBC Pig-a assay). The usefulness of the PIGRET assay as a short-term test has been confirmed in a collaborative study in Japan with 24 chemicals. One of these chemicals, diethylnitrosamine (DEN), which mainly induces liver tumors in both sexes of rats, was tested. To determine the appropriate doses, DEN was dissolved in physiological saline and administered orally with a single dose to male 8-week-old Sprague-Dawley rats in a preliminary dose-range finding study...
November 15, 2016: Mutation Research
https://www.readbyqxmd.com/read/27913578/characterization-of-egfr-t790m-l792f-and-c797s-mutations-as-mechanisms-of-acquired-resistance-to-afatinib-in-lung-cancer
#11
Yoshihisa Kobayashi, Koichi Azuma, Hiroki Nagai, Young Hak Kim, Yosuke Togashi, Yuichi Sesumi, Masato Chiba, Masaki Shimoji, Katsuaki Sato, Kenji Tomizawa, Toshiki Takemoto, Kazuto Nishio, Tetsuya Mitsudomi
Lung cancers harboring common EGFR mutations respond to EGFR tyrosine kinase inhibitors (TKIs). We previously reported that tumors with exon 18 mutations are particularly sensitive to irreversible second-generation (2G) afatinib compared with 1G-TKIs. However, data on the mechanisms of acquired resistance to afatinib are limited. We established afatinib-resistant cells by transfecting Ba/F3 cells with common or exon 18 (G719A and Del18) mutations and subjecting them to chronic exposure to increasing concentrations of afatinib...
December 2, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27907103/tbx20-is-an-essential-regulator-of-embryonic-heart-growth-in-zebrafish
#12
Steffen Just, Linda Raphel, Ina M Berger, Anja Bühler, Mirjam Keßler, Wolfgang Rottbauer
The molecular mechanisms that regulate cardiomyocyte proliferation during embryonic heart growth are not completely deciphered yet. In a forward genetic N-ethyl-N-nitrosourea (ENU) mutagenesis screen, we identified the recessive embryonic-lethal zebrafish mutant line weiches herz (whz). Homozygous mutant whz embryos display impaired heart growth due to diminished embryonic cardiomyocyte proliferation resulting in cardiac hypoplasia and weak cardiac contraction. By positional cloning, we found in whz mutant zebrafish a missense mutation within the T-box 20 (Tbx20) transcription factor gene leading to destabilization of Tbx20 protein...
2016: PloS One
https://www.readbyqxmd.com/read/27884590/physical-activity-induced-protection-against-breast-cancer-risk-associated-with-delayed-parity
#13
Kathleen M Sturgeon, Aaron Schweitzer, John J Leonard, Deirdre K Tobias, Ying Liu, Elizabeth Cespedes Feliciano, Vasanti S Malik, Amit Joshi, Bernard Rosner, Bart C De Jonghe
Epidemiological evidence indicates that physical activity between menarche and first pregnancy is associated with a lower risk of breast cancer among women with at least 20years between these reproductive events. The mechanism by which physical activity during this interval confers protection is unknown. This study used a novel animal model to assess potentially protective effects of physical activity on tumor development in delayed parity. Thirty-six female Sprague Dawley rats received an i.p. injection of 50mg/kg N-methyl-N-nitrosourea (MNU) at 5weeks of age...
February 1, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/27880821/inhibition-of-the-tgf%C3%AE-pathway-enhances-retinal-regeneration-in-adult-zebrafish
#14
Christoph Tappeiner, Ellinor Maurer, Pauline Sallin, Thomas Bise, Volker Enzmann, Markus Tschopp
In contrast to the mammalian retina, the zebrafish retina exhibits the potential for lifelong retinal neurogenesis and regeneration even after severe damage. Previous studies have shown that the transforming growth factor beta (TGFβ) signaling pathway is activated during the regeneration of different tissues in the zebrafish and is needed for regeneration in the heart and the fin. In this study, we have investigated the role of the TGFβ pathway in the N-methyl-N-nitrosourea (MNU)-induced chemical model of rod photoreceptor de- and regeneration in adult zebrafish...
2016: PloS One
https://www.readbyqxmd.com/read/27866331/photoreceptor-degeneration-by-intravitreal-injection-of-n-methyl-n-nitrosourea-mnu-in-rabbits-a-pilot-study
#15
Sarah Rösch, Claudia Werner, Frank Müller, Peter Walter
BACKGROUND: Pilot study on the attempt to induce selective photoreceptor degeneration in the rabbit eye by intravitreal injection of MNU, facing the difficulties of the evaluation of retinal degeneration by different in-vivo and in-vitro methods in such a large eye animal model. METHODS: Eight pigmented Chinchilla Bastard rabbits were injected intravitreally with MNU (1 × 1mg/kg body weight (BW), 1 × 2mg/kg BW, 3 × 3mg/kg BW, 1 × 4mg/kg BW, 1 × 6mg/kg BW, and 1 × DMSO + PBS as control)...
November 19, 2016: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/27862073/n-methyl-n-nitrosourea-induces-retinal-degeneration-in-the-rat-via-the-inhibition-of-nf-%C3%AE%C2%BAb-activation
#16
Yu Xiong, Hong-Pei Ji, Wei-Tao Song, Ye-Wei Yin, Chao-Hua Xia, Bei Xu, Yi Xu, Xiao-Bo Xia
Retinitis pigmentosa (RP) is a group of inherited neurodegenerative diseases characterized by the loss of photoreceptor cells through apoptosis. N-methyl-N-nitrosourea (MNU) is an alkylating toxicant that induces photoreceptor cell death resembling hereditary RP. This study aimed to investigate the role of nuclear factor κB (NF-κB) in MNU-induced photoreceptor degeneration. Adult rats received a single intraperitoneal injection of MNU (60 mg/kg bodyweight). Hematoxylin and eosin staining demonstrated progressive outer nuclear layer (ONL) loss after MNU treatment...
December 2016: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/27848995/a-novel-enu-induced-ankyrin-1-mutation-impairs-parasite-invasion-and-increases-erythrocyte-clearance-during-malaria-infection-in-mice
#17
Hong Ming Huang, Denis C Bauer, Patrick M Lelliott, Andreas Greth, Brendan J McMorran, Simon J Foote, Gaetan Burgio
Genetic defects in various red blood cell (RBC) cytoskeletal proteins have been long associated with changes in susceptibility towards malaria infection. In particular, while ankyrin (Ank-1) mutations account for approximately 50% of hereditary spherocytosis (HS) cases, an association with malaria is not well-established, and conflicting evidence has been reported. We describe a novel N-ethyl-N-nitrosourea (ENU)-induced ankyrin mutation MRI61689 that gives rise to two different ankyrin transcripts: one with an introduced splice acceptor site resulting a frameshift, the other with a skipped exon...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27815463/effects-of-dietary-xanthophylls-canthaxanthin-and-astaxanthin-on-n-methyl-n-nitrosourea-induced-rat-mammary-carcinogenesis
#18
Takashi Yuri, Katsuhiko Yoshizawa, Yuko Emoto, Yuichi Kinoshita, Michiko Yuki, Airo Tsubura
BACKGROUND: Natural xanthophylls, canthaxanthin and astaxanthin are known to exhibit anticancer activity. However, the dietary effects of canthaxanthin and astaxanthin on N-methyl-N-nitrosourea (MNU)-induced mammary cancer remain controversial, and their mechanisms of action have not been clearly identified. MATERIALS AND METHODS: Three-week-old female Sprague-Dawley rats were fed a xanthophyll-free (basal diet) diet or experimental diets containing canthaxanthin or astaxanthin (0...
November 2016: In Vivo
https://www.readbyqxmd.com/read/27809286/the-development-of-a-parenteral-pharmaceutical-formulation-of-a-new-class-of-compounds-of-nitrosourea
#19
Ludmila Nikolaeva, Natalia Oborotova, Natalia Bunyatyan, Xi Zhang, Ekaterina Sanarova, Anna Lantsova, Olga Orlova, Alevtina Polozkova
Despite the rapid development of medical technologies, chemotherapy treatment still occupies an important place in clinical oncology. In this regard, the current research in this area focuses on the synthesis of new highly effective antitumor substances that have minimal side effects and the development of stable pharmaceutical formulations (PF) on their basis. In order to solve this problem, the I. Ya. Postovsky Institute of Organic Synthesis of the Ural Branch of the Russian Academy of Sciences actively sought for original substances, namely, nitrosourea (NU) derivatives, one of the most promising classes of anticancer drugs...
November 1, 2016: Pharmaceuticals
https://www.readbyqxmd.com/read/27795689/identification-and-linkage-analysis-of-a-new-rice-bacterial-blight-resistance-gene-from-xm14-a-mutant-line-from-ir24
#20
Constantine Busungu, Satoru Taura, Jun-Ichi Sakagami, Katsuyuki Ichitani
Bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo) is a chief factor limiting rice productivity worldwide. XM14, a rice mutant line resistant to Xoo, has been obtained by treating IR24, which is susceptible to six Philippine Xoo races and six Japanese Xoo races, with N-methyl-N-nitrosourea. XM14 showed resistance to six Japanese Xoo races. The F2 population from XM14 × IR24 clearly showed 1 resistant : 3 susceptible segregation, suggesting control of resistance by a recessive gene. The approximate chromosomal location of the resistance gene was determined using 10 plants with shortest lesion length in the F2 population from XM14 × Koshihikari, which is susceptible to Japanese Xoo races...
September 2016: Breeding Science
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