Selenium and Selenoprotein Deficiencies Induce Widespread Pyogranuloma Formation in Mice, while High Levels of Dietary Selenium Decrease Liver Tumor Size Driven by TGFa Public Deposited

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  • Selenium and Selenoprotein Deficiencies Induce Widespread Pyogranuloma Formation in Mice, while High Levels of Dietary Selenium Decrease Liver Tumor Size Driven by TGFα
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  • Changes in dietary selenium and selenoprotein status may influence both anti- and pro-cancer pathways, making the outcome of interventions different from one study to another. To characterize such outcomes in a defined setting, we undertook a controlled hepatocarcinogenesis study involving varying levels of dietary selenium and altered selenoprotein status using mice carrying a mutant (A37G) selenocysteine tRNA transgene (Trsp[superscript tG37]) and/or a cancer driver TGFα transgene. The use of Trsp[superscript tG37] altered selenoprotein expression in a selenoprotein and tissue specific manner and, at sufficient dietary selenium levels, separate the effect of diet and selenoprotein status. Mice were maintained on diets deficient in selenium (0.02 ppm selenium) or supplemented with 0.1, 0.4 or 2.25 ppm selenium or 30 ppm triphenylselenonium chloride (TPSC), a non-metabolized selenium compound. Trsp[superscript tG37] transgenic and TGFα/Trsp[superscript tG37] bi-transgenic mice subjected to selenium-deficient or TPSC diets developed a neurological phenotype associated with early morbidity and mortality prior to hepatocarcinoma development. Pathology analyses revealed widespread disseminated pyogranulomatous inflammation. Pyogranulomas occurred in liver, lungs, heart, spleen, small and large intestine, and mesenteric lymph nodes in these transgenic and bi-transgenic mice. The incidence of liver tumors was significantly increased in mice carrying the TGFα transgene, while dietary selenium and selenoprotein status did not affect tumor number and multiplicity. However, adenoma and carcinoma size and area were smaller in TGF alpha transgenic mice that were fed 0.4 and 2.25 versus 0.1 ppm of selenium. Thus, selenium and selenoprotein deficiencies led to widespread pyogranuloma formation, while high selenium levels inhibited the size of TGFα-induced liver tumors.
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  • Moustafa ME, Carlson BA, Anver MR, Bobe G, Zhong N, ... (2013) Selenium and Selenoprotein Deficiencies Induce Widespread Pyogranuloma Formation in Mice, while High Levels of Dietary Selenium Decrease Liver Tumor Size Driven by TGFa. PLoS ONE 8(2): e57389. doi:10.1371/journal.pone.0057389
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  • description.provenance : Approved for entry into archive by Deborah Campbell(deborah.campbell@oregonstate.edu) on 2013-04-08T17:27:53Z (GMT) No. of bitstreams: 3 license_rdf: 22765 bytes, checksum: 56265f5776a16a05899187d30899c530 (MD5) license_text: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) BobeGerdAnimalScienceSeleniumSelenoproteinDeficiencies.pdf: 771678 bytes, checksum: eb2390eddac40a5528770f61afb4edcd (MD5)
  • description.provenance : Submitted by Deborah Campbell (deborah.campbell@oregonstate.edu) on 2013-04-08T16:48:58Z No. of bitstreams: 3 license_rdf: 22765 bytes, checksum: 56265f5776a16a05899187d30899c530 (MD5) license_text: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) BobeGerdAnimalScienceSeleniumSelenoproteinDeficiencies.pdf: 771678 bytes, checksum: eb2390eddac40a5528770f61afb4edcd (MD5)
  • description.provenance : Made available in DSpace on 2013-04-08T17:27:53Z (GMT). No. of bitstreams: 3 license_rdf: 22765 bytes, checksum: 56265f5776a16a05899187d30899c530 (MD5) license_text: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) BobeGerdAnimalScienceSeleniumSelenoproteinDeficiencies.pdf: 771678 bytes, checksum: eb2390eddac40a5528770f61afb4edcd (MD5) Previous issue date: 2013-02-27

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