International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 195 - MRI FOLLOW-UP OF THE ANTI-TUMORAL EFFECT OF HYSTONE DEACETYLASE INHIBITORS (HDACIS) IN A GAMMA-IRRADIATED MOUSE LYMPHOMA MODEL

Herranz M
Spanish National Cancer Centre

Co-Authors: de la Cueva E, Villar-Garea A, Fraga MF, Martín-Caballero J, Esteller M
Institutions: Spanish National Cancer Centre

Pharmacological manipulation of chromatin remodelling process by histone deacetylase (HDAC) inhibitors might develop into a potent and specific strategy for the treatment of cancer. Alterations in histone acetylation may lead to changes in chromatin structure and transcriptional deregulation of genes. A protocol to induce thymic lymphomas in mice has been developed by gamma irradiation. Gamma irradiation in a whole body way induces thymic lymphomas in 90% of treated mice from C57BL/6J strain. Our goal is to analyze the effect of hystone deacetylase inhibitors in the tumor initiation and progression. One hundred animals were irradiated and nine hystone deacetilases inhibitors assays were evaluated. Intraperitoneal inoculation of six drugs (Valproate, Butyrate (2 different doses), TSA, SAHA, LAQ (2 different doses) and MS275) was performed, 10 animals each (5 males and 5 females) and one control assay: PBS (Phophate Buffer Saline) inoculation. Each mouse was imaged with a periodicity of 2 weeks after the establishment of the treatment using conventional T2-weighted fast spin echo sequences. Significant decrease of tumor size has been found with one of the HDAC inhibitor. The survival curves show us the protective effects of HDACi in the development of thymic lymphomas. Detailed pathological analysis discard toxicity of these compounds. HDAC inhibitors remain one of the most promising class of new anticancer agents. Further studies are currently in progress to delineate the optimal dosage and the duration of therapy.


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