Inhibition of topoisomerase IIa sensitizes XXXX cells to ionizing radiation by diminishing DNA repair.

@entity1 @entity135 @entity5 @entity957 @entity2879
Despite the high efficiency of ionizing radiation (IR) to inactivate @entity5 in general, an appreciable number of individual @entity1 cannot be cured by standard IR. @entity135 are not likely to be cured even by high-dose radiotherapy or chemotherapy. Accordingly, combined therapy is one of the most applicable strategies. Topoisomerase IIa is a ubiquitous enzyme that removes knots and tangles from the genetic material by generating and subsequently resealing of transient double-strand breaks. Due to its unique mechanism of action, topoisomerase IIa is the target of many chemotherapeutic agents such as @entity2879 . The aim of the present study is to examine the effect of inhibiting topoisomerase IIa by @entity2879 on the response of @entity957 to IR. Results of the present study demonstrated a radiosensitizing effect for the topoisomerase IIa inhibitor @entity2879 on exponentially growing @entity957 ( @entity1 ) cell line especially at low radiation doses. This effect was found to be due to inhibition, by @entity2879 , of the repair of radiation-induced DNA damage. Cell cycle studies showed that the concentration of @entity2879 that sensitized the cells to radiation had no effect on the distribution of cells at different phases of the cell cycle. Synchronization of @entity1 cells in different cell cycle phases revealed that proliferating G1 and G2 cells are responsible for sensitization of cells at low doses of ionizing radiation. It might, therefore, be concluded that topoisomerase II enzyme may be involved in the repair of radiation-induced DNA damage and consequently its inhibition constitute a strategy for sensitizing @entity5 cells to ionizing radiation.
