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The novel DNA methylation inhibitor zebularine is effective against the development of murine T-cell lymphoma

  1. Author:
    Herranz, M.
    Martin-Caballero, J.
    Fraga, M. F.
    Ruiz-Cabello, J.
    Flores, J. M.
    Desco, M.
    Marquez, V.
    Esteller, M.

  2. Author Address

    Spanish Natl Canc Ctr, Canc Epigenet Lab, Madrid 28029, Spain. Spanish Natl Canc Ctr, Anim Facil Unit, Madrid 28029, Spain. Univ Complutense Madrid, Sch Vet, Inst Estudios Biofuncionales, Madrid, Spain. Univ Complutense Madrid, Sch Vet, Dept Pathol, Madrid, Spain. Univ Hosp Gregorio Maranon, Dept Expt Surg, Med Image Lab, Madrid, Spain. NCI, Med Chem Lab, NIH, Frederick, MD 21701 USA Esteller, M, Spanish Natl Canc Ctr, Canc Epigenet Lab, Melchor Fernandez Almagro 3, Madrid 28029, Spain
    1. Year: 2006
    2. Date: FEB 1
  2. Journal: Blood
    1. 107
    2. 3
    3. Pages: 1174-1177
  4. Type of Article: Article
  1. Abstract:

    Gene silencing by CpG island promoter hypermethylation has awakened the interest for DNA demethylating agents as chemotherapy drugs. Zebularine (1-[beta-D-ribofuranosil]-1,2-dihydropyrimidin-2-1) 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 and 5.5 months. In contrast, 40% (12 of 30) of zebularine-treated animals were still alive after 1 year (Kaplan-Meier P < .001). 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 nonirradiated 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 antitumor activity and little toxicity

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External Sources

  1. View record in Web of Science®
  2. WOS: 000234991600055

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