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

PERONA M; IBAÑEZ I; ROSEMBLIT C; GRISSI C; CAMPOS HAEDO M; THOMASZ L; DAGROSA MA; CREMASCHI G; JUVENAL G,

Mar del Plata

Congreso; LXVI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2021

Introduction: Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies in humans. Novel strategies to control it, like radiotherapy as altered fractionation or in combination with chemotherapy, are therefore necessary. We have previously shown an increase in the DNA damage by the histone deacetylase inhibi tors (HDACi) valproic acid (VA) in irradiated ATC cells. HDACi have emerged recently as promising anticancer agents. Their antitumor activity has been linked to their ability to induce gene expression through acetylation of histone and nonhistone proteins. DNA dou ble-strand breaks (DSBs) are the lethal lesions induced by ioniz ing radiation and the majority is repaired by either non-homologous end-joining (NHEJ) or homologous recombination (HR). The modu lation of DNA damage repair by HDACi could be one of the under lying mechanisms for the radiosensitizing effect in cancer cell lines. Objectives: To study the mechanism of the radiosensitizing effect of valproic acid in an anaplastic thyroid cancer cell line (8505c). Methods: Cells were incubated with 1 mM VA and irradiated with a source of gamma rays. Radiation response was analyzed by clo nogenic assay. Gene expression was assessed by real time PCR at 30 min and 4 hours after irradiation. Results: A radiosensitizing effect was observed with a reduction of survival fraction at 2 Gy from 0.28 to 0.20 in the treated cells (p