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Blood, 1 February 2006, Vol. 107, No. 3, pp. 1174-1177. Prepublished online as a Blood First Edition Paper on October 20, 2005; DOI 10.1182/blood-2005-05-2033. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: 2005-05-2033v1 107/3/1174    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Herranz, M. Articles by Esteller, M. Search for Related Content PubMed PubMed Citation Articles by Herranz, M. Articles by Esteller, M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 20, 2005 Accepted September 25, 2005 The novel DNA methylation inhibitor zebularine is effective against the development of murine T-cell lymphoma Michel Herranz, Juan Martin-Caballero, Mario F Fraga, Jesus Ruiz-Cabello, Juana M Flores, Manuel Desco, Victor Marquez, and Manel Esteller* Cancer Epigenetics Laboratory, Spanish National Cancer Centre (CNIO), Madrid, Spain Animal Facility Unit, Spanish National Cancer Centre (CNIO), Madrid, Spain Instituto de Estudios Biofuncionales, Complutense University of Madrid, Madrid, Spain Pathology Department, School of Veterinary, Complutense University of Madrid, Madrid, Spain Medical Image Laboratory, Department of Experimental Surgery, University Hospital Gregorio Maranon, Madrid, Spain Laboratory of Medical Chemistry, National Cancer Institute, Frederick, Maryland, USA * Corresponding author; email: mesteller{at}cnio.es. Gene silencing by CpG island promoter hypermethylation has awakened the interest for DNA demethylating agents as chemotherapy drugs. Zebularine [1-(-D-ribofuranosil)-1,2-dihydropyrimidin-2-one) has been recently described as a new DNA methylation inhibitor. Here we have studied its effects in a mouse model of radiation-induced lymphomagenesis using Nuclear Magnetic Resonance (NMR) and Positron Emission Tomography (PET). All control animals presented large thymic T-lymphomas and died between 4-5.5 months. In contrast, 40% (12 of 30) of zebularine-treated animals were still alive after one year (Kaplan-Meier p< 0.0001). NMR and PET imaging showed that surviving animals presented a thymus structure/volume similar to normal mice of the same age. Most important, zebularine demonstrated a complete lack of toxicity in non-irradiated control mice. DNA hypomethylation induced by zebularine occurred in association with depletion in extractable DNA methyltransferase 1 protein. Thus, our data support the role of zebularine as a DNA demethylating agent with antitumoral activity and little toxicity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. H. Beumer, J. L. Eiseman, R. A. Parise, E. Joseph, J. L. Holleran, J. M. Covey, and M. J. Egorin Pharmacokinetics, Metabolism, and Oral Bioavailability of the DNA Methyltransferase Inhibitor 5-Fluoro-2'-Deoxycytidine in Mice Clin. Cancer Res., December 15, 2006; 12(24): 7483 - 7491. [Abstract] [Full Text] [PDF]

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