Comparison of initial chromosome break repair in cells irradiated with high and low LET radiation

The aim of this research is to determine the earliest biological effects at the chromosome level by high LET heavy ion radiation compared to those by X-rays in normal human cells (HFL III). We measured the number of chromosome breaks by the fusion-induced premature chromosome condensation (PCC) assay. This assay is a cytogenetic method which can visualize chromosomes in inter-phase cells. As radiation sources, we used x-rays, carbon ions (70 keV/um), neon ions (70 keV/um, 200 keV/um), silicon ions (70 keV/um, 200 keV/um), and iron ions (200 keV/um). For all the PCC experiments, plateau cells (G0/G1 phase) were irradiated at 2Gy. In the process of fusion-based PCC induction, cells have to be incubated at 37C, and the repair of DSBs can occur during this period. In order to detect chromosome breaks induced by irradiation at the earliest time point, we applied wortmannin (WM) to inhibit most of the DNA-PK dependent NHEJ type DSB repair during the incubation.In the case of X-rays about one half of the initial chromosome breaks were repaired, while almost no rejoining of initial breaks was observed in cells irradiated with silicon and iron particles. A correlation can be observed between the initial repair and the actual energy of the incoming particles, especially when the LET was 70 keV/um. When the LET was around 200 keV/um, the chromosome/DSB repair was almost fully inhibited irrespective of the kind of nuclides and the incoming energy. Our present study seems to substantiate the idea of complex or dirty DSB induced by high LET radiation. Although the number of induced chromosome breaks is low, the complex DNA damages would lead to substantially impaired initial part of NHEJ repair and eventual severe biological consequences.Our results provide useful insight on the initial stage of DNA DSB/chromosome damage and repair induced by high LET heavy ions.13th International Congress of Radiation Researc