title: Effects of Valproic Acid on Radiation-Induced Chromosomal Aberrations in Human Lymphocytes.
abstract: One of the most widely employed histone deacetylases inhibitors in the clinic is the valproic acid (VA), proving to have a good tolerance and low side effects on human health. VA induces changes in chromatin structure making DNA more susceptible to damage induction and influence DNA repair efficiency. VA is also proposed as a radiosensitizing agent. To know if VA is suitable to sensitize human lymphocytes γ-irradiationin vitro, different types of chromosomal aberrations in the lymphocytes, either in the absence or presence of VA, were analyzed. For this purpose, blood samples from four healthy donors were exposed to γ-rays at a dose of 1.5 Gy and then treated with two different doses of VA (0.35 or 0.70 mM). Unstable and stable chromosomal aberrations were analyzed by means of fluorescencein situhybridization. Human lymphocytes treated with VA alone did not show any increase in the frequency of chromosomal aberrations. However, a moderate degree of sensitization was observed, through the increase of chromosomal aberrations, when 0.35 mM VA was employed after γ-irradiation, whereas 0.70 mM VA did not modify chromosomal aberration frequencies. The lower number of chromosomal aberrations obtained when VA was employed at higher dose after γ-irradiation, could be related to the induction of a cell cycle arrest, a fact that should be taken into consideration when VA is employed in combination with physical or chemical agents.
authors.affiliation: Clemente Estable Biological Research Institute, Montevideo, Uruguay; Laboratoire de Dosimétrie Biologique, Institut de Radiobiologie et de Sureté Nucléaire, Fontenay-Aux-Roses, France; Department of Genetics, Clemente Estable Biological Research Institute, Montevideo, Uruguay.
authors.forename: María Vittoria
authors.initials: MV
authors.lastname: Di Tomaso
authors.affiliation: Laboratoire de Dosimétrie Biologique, Institut de Radiobiologie et de Sureté Nucléaire, Fontenay-Aux-Roses, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Gregoire
authors.affiliation: Clemente Estable Biological Research Institute, Montevideo, Uruguay; Epigenetics and Genomic Instability Laboratory, Clemente Estable Biological Research Institute, Montevideo, Uruguay.
authors.forename: Wilner
authors.initials: W
authors.lastname: Martínez-López
keywords: Biological dosimetry; chromosomal aberrations; histone acetylation; histone deacetylase inhibitors; ionizing radiation; valproic acid