Mechanisms of the DNA Damage Repair Gene Work on Elevated α/β ratio after Hypofractionated Radiotherapy for Prostate Cancer

Abstract

Abstract Purpose: Our previous study showed that the linear quadratic (LQ) model appeared to be inappropriate for high doses per fraction owing to α/β ratio tending to become higher when the dose per fraction increased. In order to verify this conclusion, we explored the mechanisms for the elevated α/β ratio after hypofractionated radiotherapy. Materials and Methods: We selected two prostate cancer cell lines DU145 and PC3: 1) Draw the cell survival curve to calculate the α/β ratio, and then use biological effective dose (BED) formula to convert fractionated radiation dose into equivalent single hypofractionated radiation dose (calculated values) comparing with that on the survival curve (actual values). 2) Western Blot and laser confocal immunofluorescence were used to detect the expression of γ-H2AX and RAD51 after different fractionated modes of radiation at different time points. Results: 1) When fractionated radiation dose was converted into equivalent single hypofractionated radiation dose, the ability of hypofractionated radiation was overestimated. If a larger α/β ratio is used, the discrepancy tended to become smaller. 2) Compared with fractionated radiation, the results showed that the expression of γ-H2AX was higher after 30min, 6 h and 24h after single hypofractionated radiation. Meanwhile, the expression of RAD51 lasted for 24 hours and the DNA damage still existed in single hypofractionated radiation. 3) The results also showed that the expression of γ-H2AX decreased slightly after 24 hours of fractionated radiation compared with that of 6 hours, and there was no difference in single hypofractionated radiation between 6 hours and 24 hours. Conclusions: The results of this study suggest that after single hypofractionated radiation, the irreparable damage in cells increased (that is, α value increased), and some repairable sublethal damage (β value) was converted into irreparable damage (α value). When α value increased and β value decreased, the ratio increased.