Room: Karl Dean Ballroom A1
Purpose: To assess the importance of DNA double strand break (DSB) repair defects on cell radiosensitivity in helium and carbon ion beams of varying linear energy transfer (LET).
Methods: We selected a number of cancer cell lines based upon their deficiency and proficiency statuses in the non-homologous end joining (NHEJ) and homologous recombination (HR) DSB repair pathways: M059K and M059J glioblastoma cells (extracted from the same tumor, but M059J is deficient in NHEJ), H1299 non-small cell lung cancer cells (upregulated HR), and as reference cell lines, H460 large cell lung cancer and BxPC3 pancreatic adenocarcinoma cells; and performed clonogenic survival assays in helium and carbon ion beams of varying LETs. The cells were exposed to un-modulated ion beams with nominal energies of 150 MeV/u (helium) and 290 MeV/u (carbon), using energy degraders to achieve LETs ranging from 2.2 to 60 keV/Î¼m. We exposed the cells to clinical 6 MV x-rays at a depth of 10 cm in water for reference. Clonogenic survival was then used to determine the relative biological effectiveness (RBE) for each cell line and LET at 10% survival fraction.
Results: We observed minimal increases in RBE with LET for the NHEJ deficient cells (only 1.34 Â± 0.05 for M059J cells at 60 keV/Î¼m), while observing large increases in RBE with LET for the reference cell lines (2.2 Â± 0.2 for M059K, 1.78 Â± 0.05 for H460 and 3.1 Â± 0.6 for BxPC3 at 60 keV/Î¼m). However, the NHEJ deficient cells were the most radiosensitive to all LETs. The cells with upregulated HR, H1299, showed a modest increase in RBE with LET (1.59 Â± 0.11 at 60 keV/Î¼m), and were the most radioresistant to all LETs.
Conclusion: Our results indicate that proficiency status in HR and NHEJ may influence how cell radiosensitivity varies with light ion LET.