TITLE

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

AUTHOR(S)
Moustafa, Mohamed E.; Carlson, Bradley A.; Anver, Miriam R.; Bobe, Gerd; Zhong, Nianxin; Ward, Jerrold M.; Perella, Christine M.; Hoffmann, Victoria J.; Rogers, Keith; Combs Jr, Gerald F.; Schweizer, Ulrich; Merlino, Glenn; Gladyshev, Vadim N.; Hatfield, Dolph L.
PUB. DATE
February 2013
SOURCE
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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 (TrsptG37) and/or a cancer driver TGFα transgene. The use of TrsptG37 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. TrsptG37 transgenic and TGFα/TrsptG37 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 TGFα 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.
ACCESSION #
87625418

 

Related Articles

  • 2-Amino-3-Methylimidazo[4,5-f]Quinoline (IQ) Promotes Mouse Hepatocarcinogenesis by Activating Transforming Growth Factor-β and Wnt/β-Catenin Signaling Pathways. Xie, Xiao-Li; Wei, Min; Kakehashi, Anna; Yamano, Shotaro; Tajiri, Masaki; Wanibuchi, Hideki // Toxicological Sciences;Feb2012, Vol. 125 Issue 2, p392 

    The purposes of the present study were to investigate the modifying effects of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), a genotoxic carcinogen produced during cooking of protein-rich foods, and elucidate underlying mechanisms in a two-stage hepatocarcinogenesis mice model. Six-week-old...

  • Peritoneal fibrosis is mouse strain dependent. Bodenham, Tanya; Topley, Nicholas; Fraser, Donald // Nephrology Dialysis Transplantation;Aug2013, Vol. 28 Issue 8, p1966 

    No abstract available.

  • Contrasting roles of dietary selenium and selenoproteins in chemically induced hepatocarcinogenesis. Kasaikina, Marina V.; Turanov, Anton A.; Avanesov, Andrei; Schweizer, Ulrich; Seeher, Sandra; Bronson, Roderick T.; Novoselov, Sergey N.; Carlson, Bradley A.; Hatfield, Dolph L.; Gladyshev, Vadim N. // Carcinogenesis;May2013, Vol. 34 Issue 5, p1089 

    Selenium (Se) has long been known for its cancer prevention properties, but the molecular basis remains unclear. The principal questions in assessing the effect of dietary Se in cancer are whether selenoproteins, small molecule selenocompounds, or both, are involved, and under which conditions...

  • Dietary selenium affects intestinal development of Eimeria papillata in mice. Dkhil, Mohamed; Abdel-Baki, Abdel; Wunderlich, Frank; Sies, Helmut; Al-Quraishy, Saleh // Parasitology Research;Jan2014, Vol. 113 Issue 1, p267 

    Here, we investigated the effect of the trace element selenium (Se) on course and outcome of Eimeria-paplllata-induced coccidiosis in mice. Male mice were fed on Se-adequate (0.15 ppm), Se-deficient, and Se-high diets (1.0 ppm) for 6 weeks. Mice were orally infected with 1,000 oocysts. The...

  • Selenoproteins reduce susceptibility to DMBA-induced mammary carcinogenesis. Hudson, Tamaro S.; Carlson, Bradley A.; Hoeneroff, Mark J.; Young, Heather A.; Sordillo, Lorraine; Muller, William J.; Hatfield, Dolph L.; Green, Jeffrey E. // Carcinogenesis;Jun2012, Vol. 33 Issue 6, p1 

    Selenium is an essential micronutrient in the diet of humans and other mammals. Based largely on animal studies and epidemiological evidence, selenium is purported to be a promising cancer chemopreventive agent. However, the biological mechanisms by which chemopreventive activity takes place are...

  • TGFβ-mediated upregulation of hepatic miR-181b promotes hepatocarcinogenesis by targeting TIMP3. Wang, B.; Hsu, S.-H.; Majumder, S.; Kutay, H.; Huang, W.; Jacob, S. T.; Ghoshal, K. // Oncogene;3/25/2010, Vol. 29 Issue 12, p1787 

    To identify microRNAs (miRNAs) that may have a causal role in hepatocarcinogenesis, we used an animal model in which C57BL/6 mice fed choline-deficient and amino acid defined (CDAA) diet develop preneoplastic lesions at 65 weeks and hepatocellular carcinomas after 84 weeks. miRNA expression...

  • The Complexities of TGF-β Action During Mammary and Squamous Cell Carcinogenesis. Connolly, Erin C.; Akhurst, Rosemary J. // Current Pharmaceutical Biotechnology;Dec2011, Vol. 12 Issue 12, p2138 

    Many advanced tumors produce excess amounts of Transforming Growth Factor- (TGF-β), which is a potent growth inhibitor of normal epithelial cells. However, in tumors its homeostatic action on cells can be diverted along several alternative pathways. Thus, TGF-β signaling has been reported...

  • Akt1 deletion prevents lung tumorigenesis by mutant K-ras. Hollander, M C; Maier, C R; Hobbs, E A; Ashmore, A R; Linnoila, R I; Dennis, P A // Oncogene;4/14/2011, Vol. 30 Issue 15, p1812 

    K-ras mutations are associated with smoking-induced lung cancer and poor clinical outcomes. In mice, K-ras mutations are sufficient to induce lung tumors, which require phosphoinoside-3-kinase (PI3K) and further downstream, mammalian target of rapamycin (mTOR) activation. However, the roles of...

  • A Transposon-Based Analysis of Gene Mutations Related to Skin Cancer Development. Quintana, Rita M; Dupuy, Adam J; Bravo, Ana; Casanova, M Llanos; Alameda, Josefa P; Page, Angustias; Sánchez-Viera, Miguel; Ramírez, Angel; Navarro, Manuel // Journal of Investigative Dermatology;Jan2013, Vol. 133 Issue 1, p239 

    Nonmelanoma skin cancer (NMSC) is by far the most frequent type of cancer in humans. NMSC includes several types of malignancies with different clinical outcomes, the most frequent being basal and squamous cell carcinomas. We have used the Sleeping Beauty transposon/transposase system to...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics