Radiosensitisation enhancement effect of BrUdR and Ta2O5 NSPs in combination with 5-Fluorouracil antimetabolite in kilovoltage and megavoltage radiation

This article demonstrates in vitro a synergistic effect on 9L gliosarcoma cells when exposed to bromodeoxyuridine (BrUdR) and a low concentration (100 times lower than the IC50) of 5-Fluorouracil (5-FU), in combination with x-ray irradiation. The synergy is brought about by several important factors including the x-ray beam energy, atomic number of the BrUdR (Z = 35), effectiveness of 5-FU in reducing the available repair processes and distribution of the BrUdR in and around the 9L cells (32% of the total substitution of BrUdR for thymidine into nucleus DNA). Our results show that the synergistic effect, evident in an optimised 125 kVp x-ray field, leads to a radiosensitisation enhancement ratio at the 10% survival level (SER10%) of 2.11. We highlight the importance of the aforementioned factors by similarly performed experiments for higher Z (Z = 73) tantalum pentoxide nano-structured particles (Ta2O5 NSPs) that are substituted for the BrUdR in larger concentration (~10 times). In the Ta2O5 NSPs experiments, no synergistic effect is observed in the kVp irradiation with optimal energy spectrum even though the effective Z and NSP concentration is much higher than for BrUdR. All experiments were repeated using a MV x-ray irradiation field and no synergistic effect is observed for either the BrUdR or Ta2O5 case. We therefore hypothesise that the synergistic outcome is due to more drastic and complex damages induced by BrUdR under the exposure of kVp radiation. Such damages are achieved by the localisation of the BrUdR in the DNA and the high LET (very short range) secondary electrons in combination with the 5-FU. In order to achieve similar synergistic effects in the more clinically relevant x-ray energy field the concentration of the high Z material needs to be greater in order to create a higher LET electron environment.