Repair of DNA double-strand breaks as a determinant of RBE of alpha particles.

The role of repair of DNA double-strand breaks (dsb) in the determination of the RBE-value of alpha particles was studied using the temperature conditional radiosensitive diploid yeast mutant rad 54-3. This mutant is proficient in the repair of dsb at the permissive temperature of 23 degrees C at which it yields a shouldered survival curve, but it is dsb repair-deficient at the restrictive temperature of 36 degrees C at which it yields an exponential survival curve. At the permissive temperature the rad 54-3 mutant also shows liquid holding recovery of colony forming ability as a function of the liquid holding period. Thus, with this mutant it is possible to obtain survival curves involving no repair of dsb (immediate plating, 36 degrees C), partial repair of dsb (immediate plating, 23 degrees C) and gradually increasing levels of dsb repair by delayed plating after liquid holding periods of 24, 48 and 72 h. The RBE-values of densely ionizing 3.5 MeV alpha particles for cell killing relative to sparsely ionizing 30 MeV electrons have been determined as a function of the level of dsb repair. It is shown that the RBE-value is low and independent of dose when no repair of dsb is involved, whereas it becomes gradually larger with a gradual increase in the level of dsb repair.