DOWNREGULATION OF DNA DAMAGE REPAIR GENES BY VALPROIC ACID RADIOSENSITIZE ANAPLASTIC THYROID CANCER CELLS

IBAÑEZ IL; ROSEMBLIT C ; GRISSI C; MATEO N CAMPOS HAEDO; THOMASZ, LISA; DAGROSA, MARÍA ALEJANDRA; CREMASCHI GA; DURAN H; JUVENAL GJ

Virtual

Congreso; Reunión conjunta SAIC.SAIC.SAAFE.NANOMED.AR; 2021

Sociedad Argentina de Investigaciones Clínicas

aggressive malignancies in humans. Novel strategies to controlit, like radiotherapy as altered fractionation or in combination withchemotherapy, are therefore necessary. We have previously shownan increase in the DNA damage by the histone deacetylase inhibitors(HDACi) valproic acid (VA) in irradiated ATC cells. HDACi haveemerged recently as promising anticancer agents. Their antitumoractivity has been linked to their ability to induce gene expressionthrough acetylation of histone and nonhistone proteins. DNA double-strand breaks (DSBs) are the lethal lesions induced by ionizingradiation and the majority is repaired by either non-homologousend-joining (NHEJ) or homologous recombination (HR). The modulationof DNA damage repair by HDACi could be one of the underlyingmechanisms for the radiosensitizing effect in cancer cell lines.Objectives: To study the mechanism of the radiosensitizing effectof valproic acid in an anaplastic thyroid cancer cell line (8505c).Methods: Cells were incubated with 1 mM VA and irradiated witha source of gamma rays. Radiation response was analyzed by clonogenicassay. Gene expression was assessed by real time PCRat 30 min and 4 hours after irradiation. Results: A radiosensitizingeffect was observed with a reduction of survival fraction at 2 Gyfrom 0.28 to 0.20 in the treated cells (p