DNA damage induced by radiation of different linear energy transfer: initial fragmentation

Purpose: To investigate DNA fragmentation as a function of linear energy tr ansfer (LET) after exposure to accelerated ions in the LET range 40-225 keV /mu m. Materials and methods: Fragmentation patterns of double-stranded DNA in the range 5 kilobasepairs (kbp) to 5.7 megabasepairs (Mbp) were analysed after irradiation of low-passage GM 5758 normal human fibroblast cells with Co-6 0-photons, helium ions at. 40 keV/mu m and high-LET nitrogen ions between 8 0 and 225 keV/mu m. Two separate pulsed-field gel electrophoresis protocols were used, optimized for separation of 1-6 Mbp and 5 kbp to 1.5 Mbp, fragm ents. Results: An increased probability of formation of short and medium-sized DN A fragments was revealed following high-LET irradiation. The DNA double-str and break (dsb) induction yields were, respectively, 5.8 and 6.9-8.8 x 10(- 9) dsb bp(-1) Gy(-1) for Co-60-photons and ions. The ion yields were some 8 0 110% higher than those calculated according to a conventional approach, d isregarding the fragment distributions. For photons, the yield was 13% high er. The corresponding relative biological effectiveness (RBE) of dsb induct ion was in the range 1.2-1.5. Conclusions: A significant non-random contribution to the number of dsb aft er irradiation with high-LET was confirmed by detailed fragment analysis us ing pulsed-field gel electrophoresis. The LET had a strong influence on the initial DNA fragment distribution, and hence also on the induction yields measured. However, when the LET was increased to the highest values studied for nitrogen ions, the yield decreased slightly.