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The Importance of DNA Double Strand Break Repair Defects to Cell Radiosensitivity in Helium and Carbon Ion Beams

D Flint1 , C Mcfadden1 , S Bright1 , D Yoon1 , S Kodaira2 , T Konishi2 , G Sawakuchi1*, (1) MD Anderson Cancer Center, Houston, Texas, USA; (2) National Institute of Radiological Sciences, Chiba, Japan


(Tuesday, 7/31/2018) 1:45 PM - 3:45 PM

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/μm. 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 ± 0.05 for M059J cells at 60 keV/μm), while observing large increases in RBE with LET for the reference cell lines (2.2 ± 0.2 for M059K, 1.78 ± 0.05 for H460 and 3.1 ± 0.6 for BxPC3 at 60 keV/μm). 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 ± 0.11 at 60 keV/μm), 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.


Radiobiology, RBE, LET


TH- Radiobiology(RBio)/Biology(Bio): RBio- Particle therapy- Carbon ion

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