by Herranz, Michel, Martín-Caballero, Juan, Fraga, Mario F, Ruiz-Cabello, Jesus, Flores, Juana Maria, Desco, Manuel, Marquez, Victor and Esteller, Manel
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.
Reference:
The novel DNA methylation inhibitor zebularine is effective against the development of murine T-cell lymphoma. (Herranz, Michel, Martín-Caballero, Juan, Fraga, Mario F, Ruiz-Cabello, Jesus, Flores, Juana Maria, Desco, Manuel, Marquez, Victor and Esteller, Manel), In Blood, American Society of Hematology, volume 107, 2006.
Bibtex Entry:
@article{Herranz:2006huc,
author = {Herranz, Michel and Mart{'i}n-Caballero, Juan and Fraga, Mario F and Ruiz-Cabello, Jesus and Flores, Juana Maria and Desco, Manuel and Marquez, Victor and Esteller, Manel},
title = {{The novel DNA methylation inhibitor zebularine is effective against the development of murine T-cell lymphoma.}},
journal = {Blood},
year = {2006},
volume = {107},
number = {3},
pages = {1174--1177},
month = feb,
publisher = {American Society of Hematology},
affiliation = {Cancer Epigenetics Laboratory and the Animal Facility Unit, Spanish National Cancer Centre (CNIO), Madrid, Spain.},
doi = {10.1182/blood-2005-05-2033},
pmid = {16239434},
language = {English},
rating = {0},
date-added = {2018-03-16T12:59:02GMT},
date-modified = {2018-04-04T07:59:10GMT},
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.},
url = {http://www.bloodjournal.org/cgi/doi/10.1182/blood-2005-05-2033},
local-url = {file://localhost/Users/jruizcabello/Documents/JRC/biblio/Papers-folder/Library.papers3/Files/24/24569E88-097A-40BC-83C0-EDA6390966E0.pdf},
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uri = {url{papers3://publication/doi/10.1182/blood-2005-05-2033}}
}