Chromatin Modulation by Histone Deacetylase Inhibitors: Impact on Cellular Sensitivity to Ionizing Radiation

It is well established that cells are more sensitive to ionizing radiation during the G₂/M phase of the cell cycle when their chromatin is highly compacted. However, highly compacted chromatin is less susceptible to DNA Double Strand Breaks (DSBs) than relaxed chromatin. Therefore, it is now becoming apparent that it is the cell capacity to repair its damaged DNA and refold its chromatin into its original compacted status that primarily affects the overall cellular sensitivity to ionizing radiation. The Histone Deacetylase Inhibitors (HDACIs) are a new class of anticancer agents that relax chromatin structure by increasing the levels of histone acetylation. The effect of HDACIs on normal and cancer cells sensitivity to ionizing radiation differs. Reports have indicated that HDACIs can protect normal cells while simultaneously sensitize cancer cells to ionizing radiation. This difference may stem from the individual characteristic of the normal and cancer cells chromatin structure. This review discusses this possibility and addresses the role of HDACIs in radiation therapy.