DNA double- and single-strand breaks induced by accelerated 2+ 6+ He and N ions in human cells: relative biological effectiveness is dependent on the relative contribution of the direct ands

Abstract

Double (dsb) and single-(ssb) strand breaks induced by accelerated He 2+ ions (LET from 10 to 220 keV mum with >70 in the range of 35-55keV mum, mean LET about 40keV mum) and N6+ ions (LET 125keV mum) have been determined in three DNA substrates derived from human cells in culture. He ions were 50 more efficient than N ions to induce dsb in intact cells. In the presence of a high concentration of an OH-radical scavenger, dimethylsulphox. ide (DMSO), the dsb were reduced by a factor of 4.5 after He ions but only a factor of 1.4 after N ions, i.e. N ions were about a factor of three more efficient in a substrate where direct hits in the DNA dominated. With gamma rays DMSO gives a reduction by a factor of 3.6. In nucleoids, where the histones were removed by salt treatment, dsb induction increased 22, 18 and 12 times for gamma rays, He ions and N ions respectively. Under these conditions dsb is about 1.5-fold higher after He compared with N ions. Total number of breaks, ssb and dsb, were determined for intact cells. Compared with gamma-rays the breaks were reduced by a factor of 4 after He ions and a factor of 14 after N ions, i.e. ssb and dsb seem to be in the same range after nitrogen ions. Although our measurements do not allow an absolute determination of relative biological effectiveness (RBE) for He and N ions induced dsb, we can show that the RBE for N ions increases by a factor of 2.5 if OH radicals are removed, and decreases by a factor of 2 if most of the protection against OH radicals is removed, altogether a variation of a factor of 5. RBE for He ions, on the other hand, is almost independent of irradiation conditions.