title: Radiosensitizing effect of the histone acetyltransferase inhibitor anacardic acid on various mammalian cell lines.
abstract: Agents that enhance the effectiveness of ionizing radiation have been investigated over many decades. A relatively new group of potential radiosensitizers consists of agents that inhibit histone acetyltransferases (HATs). This study evaluated the radiosensitizing properties of the HAT inhibitor anacardic acid (AA), used at a low-toxic concentration of 100 μM in V79, SW1573 and U2OS cells. Radiation survival curves were analyzed according to the linear quadratic model. Significant radiosensitization by AA was only obtained in U2OS cells. AA significantly increased the value of the linear parameter α, but not of the quadratic parameter β, indicating fixation of potentially lethal damage and an intact repair function of sublethal damage. The increase of the α value was also observed in SW1573 cells, but was not accompanied by a significant radiosensitization. A likely explanation for the enhancement of the α value may be an increase in the amount of lethal lesions due to the compacted chromatin structure. Despite the conflicting results of the radiosensitizing effect of AA in the three cell lines tested, the ability of AA to increase the α value suggests potential advantages for clinical application.
authors.affiliation: Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Experimental Molecular Medicine, Department of Radiation Oncology, University of Amsterdam, 1100 DE Amsterdam, The Netherlands.
authors.forename: Rosemarie Ten
authors.initials: RT
authors.lastname: Cate
authors.forename: Przemek
authors.initials: P
authors.lastname: Krawczyk
authors.forename: Jan
authors.initials: J
authors.lastname: Stap
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Aten
authors.forename: Nicolaas A P
authors.initials: NA
authors.lastname: Franken