Abstract
High LET heavy ion radiation has been successfully used for radiation cancer therapy and the biological effect is known to be more significant than low LET radiation such as X-rays. Despite its biological significance, the mechanism behind the high LET effect is not fully understood. In this presentation, the reason for the severe biological effects with high LET radiation is discussed in the context of DNA double strand break (DSB) repair, specifically non homologous end joining DSB repair pathway.We found LET dependent chromosome rejoining kinetics in normal human cells irradiated with 70 keV/um carbon and 200 keV/um iron ions. Furthermore, the iron ions seem to induce non-repairable DSB/chromosome damage. Using DSB repair deficient 180BR cells (DNA ligase IV mutant), a slow chromosome repair component (after 6h post-irradiation) was uncovered by comparing the iron and carbon rejoining kinetics. The experiment with phosphospecific antibody for DNA-PKcs also showed a significant delay in the phosphorylation process of this protein in cells exposed to high LET radiation when compared to X-rays. These results indicate that high LET heavy ion radiation induces DNA damage which is much more difficult to be repaired. The usefulness of high LET radiation to uncover the new mechanistic aspect of DNA DSB repair is also evident.
