DNA double-strand break repair determines the RBE of alpha-particles.

Radiation-induced DNA double-strand breaks (dsb) were studied in Ehrlich ascites tumour cells (EATC) by sedimentation in neutral sucrose gradients at low centrifuge speed. Dsb induction was found to be linear with dose with a frequency of: ndsbmr-1D-1 = (11.7 +/- 2) x 10(-12)Gy-1 for 140 kV X-rays and ndsbmr-1D-1 = (19.1 +/- 4) x 10(-12)Gy-1 for 3.4 MeV 241Am-alpha-particles. Postirradiation incubation of cells under non-growth conditions leads to repair of dsb, reaching a maximum after trep = 24 h. More than 97 per cent of dsb were repaired after an X-ray dose of 25 Gy. The number of residual dsb was found to be a linear-quadratic function of dose: nresmr-1 = (0.0161 +/- 0.0008) x 10(-12)Gy-2D2 for X-rays and nresmr-1 = (1.2 +/- 0.7) x 10(-12)Gy-1D + (0.105 +/- 0.017) x 10(-12)Gy-2D2 for alpha-particles. Thus, after cellular repair the RBE value of alpha-particles was increased from RBE = 1.6 +/- 0.4 (induction of dsb) to a dose-dependent value of RBE = 2.7 +/- 0.4 (at 100 Gy alpha-particles) to 3.8 +/- 1.2 (at 10 Gy alpha-particles) for residual dsb. From the data presented it is concluded that residual dsb are a major cause for loss of the reproductive capacity of EATC after irradiation with X-rays as well as alpha-particles.