Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression data from B6C3F1 mice treated with 2-butoxyethanol

ABSTRACT: Mice were dosed with 2-BE (900mg/kg) or vehicle by oral gavage and sacrificied either after 4 hours of a single dose or after 7 days of daily dosing. Mice were euthanased by cervical dislocation under ketamine / acepromazine (100 mg/kg / 5 mg/kg, I.P) anesthesia. The bone marrow from the right humerus, a portion of the left lateral liver lobe and half a cross-section of the spleen were harvested and the RNA was isolated from these tissues using standard Qiagen reagents. Standard Affymetrix protocols were used for GeneChip probe preparations. 44 arrays.

ORGANISM(S): Mus musculus

SUBMITTER: Petra Koza-Taylor

PROVIDER: E-GEOD-17794 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The role of hypoxia in 2-butoxyethanol-induced hemangiosarcoma.

Laifenfeld Daphna D Gilchrist Annalyn A Drubin David D Jorge Milena M Eddy Sean F SF Frushour Brian P BP Ladd Bill B Obert Leslie A LA Gosink Mark M MM Cook Jon C JC Criswell Kay K Somps Christopher J CJ Koza-Taylor Petra P Elliston Keith O KO Lawton Michael P MP

Toxicological sciences : an official journal of the Society of Toxicology 20091007 1

To understand the molecular mechanisms underlying compound-induced hemangiosarcomas in mice, and therefore, their human relevance, a systems biology approach was undertaken using transcriptomics and Causal Network Modeling from mice treated with 2-butoxyethanol (2-BE). 2-BE is a hemolytic agent that induces hemangiosarcomas in mice. We hypothesized that the hemolysis induced by 2-BE would result in local tissue hypoxia, a well-documented trigger for endothelial cell proliferation leading to hema ...[more]

PMID: 19812364

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Project description:In this model of ventilator-induced lung injury (VILI), we compared the gene expression profile of whole lungs extracted from sponaneously breathing mice (control, c) or mouse submitted to 8 hours mechanical venitlation with 12 ml/kg tidal volume 2cmH2O of positive end expiratory pressure (PEEP) (ventilation, v). Spontaneously breathing NOD/shi mice were randomized to control (n=3) or ventilation (n=5) condition. In brief, mice were anesthetized with the injection of ketamine (65 mg/kg, ip), acepromazine (2 mg/kg, ip) and xylazine (13 mg/kg, ip)(Henry Schein Inc., Melville, NY). Once deep sedation was achieved, a tracheostomy was performed and a PE-10 cannula was inserted in the trachea and stabilized with silk ligature. Control animals were immediately sacrificied with a supra-physiological dose of ketamine (300 mg/kg, ip). For ventilated mice, the cannula was connected to a custom built Voltek rodent ventilator (Voltek Enterprises, Toronto, CA). We ventilated mice for 8 hours using 2cmH2O positive end expiratory pressure (PEEP), inflating the lungs every hour to 20 cmH2O pressure as we have previously described. (16). The chest muscle was paralyzed with the injection of pancurorium (1mg/kg, ip)(Sigma-Aldrich) in ventilated mice to avoid spontaneous breathing. Heart rate and respiratory rate was continuously monitored and additional anesthesia was provided if a >15% increase in these parameters was detected. The animal protocol was approved by the BWH Institutional Animal Care and Use Committee (protocol #04477). Ventilated animals At the end of the each experiment, the animals were sacrificed with a supra-physiological dose of ketamine (300 mg/kg, ip). Subsequently, the chest cavity was opened, and the right lung was isolated and ligated at the main bronchus.Lungs were harvested and snap frozen in liquid nitrogen for total RNA extraction. Total RNA was extracted from lungs of controls (n=3) and mice submitted to ventilation (n=5) and there gene expression profiles were compared.

Project description:20-Hydroxyecdysone (20E) is the most abundant phytoecdysteroid produced by several plant families and has been attributed with numerous pharmacological properties in animals including anabolic and immune modulating effects. However, the in vivo bioactivity of phytoecdysteroids in mammals remains ambiguous, and moreover, the mechanism of action in mammals has yet to be determined. In this study, the physiological and gene expression effects of 20E were analyzed in C57BL/6 mice given a continuous infusion of saline or 20E (5 mg/kg/day) for five or fifteen days using subcutaneously implanted Alzet® osmotic pumps. The weights of the total body, muscle groups and organs were recorded and carcass composition was determined to evaluate changes in nutrient partitioning. There was a significant increase (p = 0.01) in the weight of triceps brachii in mice treated with 20E for five days (115 +/- 8 mg) compared to mice treated with saline for five days (88 +/- 3 mg), however, there were no differences in the other measured parameters. To determine potential mechanisms of action of 20E in skeletal muscle, Illumina’s Mouse Whole Genome-6 v2.0 Expression BeadChips were used to evaluate changes in gene expression after 20E infusion. False Discovery Rate correction of microarray data did not reveal any beadtypes that were differentially expressed. Therefore, Ingenuity Pathways Analysis (IPA) was used to identify genes with the most evidence for differential expression in the context of biological functions and pathways. IPA provided evidence for 20E involvement in processes including cellular growth and proliferation and cell-to-cell signaling and interaction. Overall, the data suggests that 20E does not have potent anabolic properties. IPA identified potential lead biological processes and pathways of 20E. Total RNA was extracted from the triceps brachii of C57BL/6 mice given a continuous infusion of saline or 20E (5 mg/kg/day) for 5 or 15 days using subcutaneously implanted Alzet® osmotic pumps to evaluate gene expression effects of 20E on mouse muscle.

Dataset Information

Expression data from B6C3F1 mice treated with 2-butoxyethanol

Publications

The role of hypoxia in 2-butoxyethanol-induced hemangiosarcoma.

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