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 textless .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, volume 107, 2006.
Bibtex Entry:
@article{herranz_novel_2006,
	title = {The novel {DNA} methylation inhibitor zebularine is effective against the development of murine {T}-cell lymphoma.},
	volume = {107},
	url = {http://www.bloodjournal.org/cgi/doi/10.1182/blood-2005-05-2033},
	doi = {10.1182/blood-2005-05-2033},
	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 {textless} .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.},
	language = {English},
	number = {3},
	journal = {Blood},
	author = {Herranz, Michel and Martín-Caballero, Juan and Fraga, Mario F and Ruiz-Cabello, Jesus and Flores, Juana Maria and Desco, Manuel and Marquez, Victor and Esteller, Manel},
	month = feb,
	year = {2006},
	pmid = {16239434},
	note = {Publisher: American Society of Hematology},
	pages = {1174--1177}
}