It has been reported that beta-lapachone (beta-lap), a bioreductive anti-cancer drug, synergistically interacts with ionizing radiation and that the sensitivity of cells to beta-lap is closely related to the activity of NAD(P)H:quinone oxidoreductase 1 (NQO1). Here we report the results of our studies of mechanisms underlying the synergistic interaction of beta-lap and radiation in killing cancer cells using the DU-145 human prostate cancer cell line. The clonogenic cell death caused by the combination of radiation and beta-lap was synergistic when beta-lap was administered 0-10 h after irradiation but not when it was given before irradiation. The expression and activity of NQO1 increased significantly and remained elevated for longer than 12 h after 4 Gy irradiation, suggesting that the long-lasting elevation of NQO1 sensitized the cells to beta-lap. Studies with split-dose irradiation demonstrated that beta-lap given immediately after irradiation effectively inhibited sublethal radiation damage (SLD) repair. Taken together, these results lead us to conclude that the synergistic interaction between beta-lap and radiation in killing cells is the result of two distinct mechanisms: First, radiation sensitizes cells to beta-lap by up-regulating NQO1, and second, beta-lap sensitizes cells to radiation by inhibiting SLD repair. The combination of beta-lap and radiotherapy is potentially promising modality for the treatment of cancer in humans.
Background/Aim: The aim of the study was to investigate the dosimetric characteristics of electron beams with a tungsten functional paper (TFP) surface collimator. Materials and Methods: The circular field of 6.0 cm diameter was created with the TFP collimator put on the phantom. Depth and lateral dose profiles for 4 and 6 MeV electron beams were obtained. The characteristics of lateral dose profile, treatment diameter as width over 90% of the dose, and penumbra as width of the off-axis positions from 80% to 20% dose levels were evaluated. Results: Compared to the lead collimator, the TFP collimator generated higher surface doses, the treatment diameters were increased from 42.8 to 48.6 mm and from 40.0 to 41.4 mm, and the penumbras were reduced from 15.0 to 9.6 mm and from 16.4 to 13.0 mm for 4 and 6 MeV electron beams, respectively. Conclusion: The TFP surface collimator can provide an excellent dose distribution compared to the conventional lead collimator.
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