Abstract
Our previous investigation showed that 5-Fluorouracil (5FU) was a electron-affinic compound, which could show oxygen-mimic effects in DNA, as the result of molecular orbital calculation. The present study aimed to clarify the radiosensitization of hypoxic human lung cancer cells (H1299), which were transfected with a wild-type p53 expression vector (H1299wtp53) and mutant vector (H1299mtp53). Exponential growing cells were suspended in media with or without 5FU and then irradiated with X-rays (150 kV) in the glass tube, into which air or nitrogen gas was flowed. Cell survival was assessed with the colony formation assay. 5FU (0.1 mM) was a effective radiosensitizer toward killing of hypoxic cells irradiated with X-rays: ER(enhancement ratio) of 1.26 on H1299wtp53, 1.14 on H1299mtp53. No potentiation of aerated cells to X-irradiation killing was observed. The fluorescence intensity of foci of gammaH2AX produced in hypoxic cells after X-irradiation was enhanced in the presence of 5FU. It was suggested that hypoxic cell killing radiosensitization by 5FU correlated with the enhancement of DNA double strand breaks.
