Elevated α/β ratio after hypofractionated radiotherapy correlated with DNA damage repairment in an experimental model of prostate cancer.

Abstract

Our previous study demonstrated that the linear quadratic model appeared to be not well-suited for high dose per fraction due to an observed increase in α/β ratio as the dose per fraction increased. To further validate this conclusion, we draw the cell survival curve to calculate the α/β ratio by the clone formation experiment and then convert the fractionated radiation dose into an equivalent single hypofractionated radiation dose comparing with that on the survival curve. Western Blot and laser confocal immunofluorescence were used to detect the expression of γ-H2AX and RAD51 after different fractionated modes of radiation. We constructed a murine xenograft model, and changes in transplanted tumor volume were used to evaluate the biological effects after different fractionated radiation. The results demonstrated that when fractionated radiation dose was converted into equivalent single hypofractionated radiation dose, the effectiveness of hypofractionated radiation was overestimated. If a larger α/β ratio was used, the discrepancy tended to become smaller. γ-H2AX was higher in 24 h after a single high dose radiation than the continuous expression of the DNA repair marker RAD51. This implies more irreparable damage in a single high dose radiation compared with fractionated radiation. In the murine xenograft model, the effectiveness of hypofractionated radiation was also overestimated, and additional fractions of irradiation may be required. The conclusion is that after single hypofractionated radiation, the irreparable damage in cells increased (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.