Abstract
To clarify the roles of two major DNA double-strand break (DSB) repair pathways, i.e., non-homologous end-joining (NHEJ) and homologous recombination (HR), in hyperthermic radiosensitization, we examined chicken B lymphocyte cell line DT40 and its derivatives lacking NHEJ and/or HR. Hyperthermic radiosensitization could be seen in all of the mutants, including those lacking both NHEJ and HR. Therefore, hyperthermic radiosensitization cannot be explained simply by the inhibitory effects, if any, on typical NHEJ and/or HR alone. However, in NHEJ-defective cells, consisting of two subpopulations with distinct radiosensitivity, the radiosensitive subpopulation, which is considered cells in G1 and early S, was not sensitized: substantial sensitization was seen only in the radioresistant subpopulation, which is considered cells in late S and G2, capable of repairing DSBs through HR. This observation did not exclude possible involvement of NHEJ in G1 and early S phases and also suggested some inhibitory effects of hyperthermia on HR. Thus, partial contribution of NHEJ and HR in hyperthermic radiosensitization, especially that depending on the cell cycle stages, remains to be considered.
