DNA DOUBLE-STRAND BREAKS INDUCED BY HIGH-ENERGY NEON AND IRON IONS INHUMAN FIBROBLASTS .1. PULSED-FIELD GEL-ELECTROPHORESIS METHOD

The relative effectiveness of high-energy neon and iron ions for the p roduction of DNA double-strand breaks was measured in one transformed and one nontransformed human fibroblast cell line using pulsed-field.g el electrophoresis. The DNA released from the gel plug (fraction of ac tivity released: FAR) as well as the size distribution of the DNA ente ring the gel were used to compare the effects of the heavy-ion exposur e with X-ray exposure. Both methods gave similar results, indicating s imilar distributions of breaks over megabase-pair distances for the he avy ions and the X rays. The relative biological effectiveness (RBE) c ompared to 225 kVp X rays of initially induced DNA double-strand break s was found to be 0.85 for 425 MeV/u neon ions (LET 32 keV/mu m) and 0 .42-0.55 for 250-600 MeV/u iron ions (LET 190-350 keV/mu m). Postirrad iation incubation showed less efficient repair of breaks induced by th e neon ions and the 600 MeV/u iron ions compared to X rays. Survival e xperiments demonstrated RBE values larger than one for cell killing by the heavy ions in parallel experiments (neon: RBE = 1.2, iron: RBE = 2.3-3.0, based on D-10 values). It is concluded that either the initia l yield of DNA double-strand breaks induced by the high-energy particl es is lower than the yield for X rays, or the breaks induced by heavy ions are present in clusters that cannot be resolved with the techniqu e used. These results are confirmed in the accompanying paper (M. Lobr ich, B. Rydberg and P. Cooper, Radiat. Res. 139, 142-151, 1994).