The Effect of Radiosensitization of Gemcitabine Related to Suppression of a Repair Pathway: Examination of Mammalian Cells with Therapeutic High Energy X-rays

摘要

Gemcitabine is used in clinical chemo-radiotherapy; however, the mechanism underlying enhanced radiosensitivity by gemcitabine is not fully elucidated. We evaluated the role of gemcitabine in mammalian cell lines using a therapeutic high energy 10 MeV linac-X-ray irradiation device. Rodent cell lines CHO and xrs5 were used. A total of 5 μM gemcitabine for 24 hours was administered with or without post-X-ray irradiation. DNA double-strand breaks (DSBs) and cell enlargement were observed by using singly gemcitabine. Enhanced cell killing effects by radiotherapy were observed with gemcitabine pre-treatment in both CHO and xrs5 cells. We focused on the dynamics of phosphorylated p53-binding protein 1 (53BP1)-positive foci after irradiation. Significantly higher numbers of 53BP1 foci were observed after irradiation in gemcitabine pre-treated cells than in untreated cells. The radiosensitizing effect of gemcitabine was not suppressed in the non-homologous end joining (NHEJ) deficient xrs5 cells. We confirmed that in rodent cells the radiosensitizing effect of gemcitabine is related to suppression of a repair pathway other than NHEJ.