The Relative Biological Effect of Spread-Out Bragg Peak Protons in Sensitive and Resistant Tumor Cells

The Relative Biological Effect of Spread-Out Bragg Peak Protons in Sensitive and Resistant Tumor Cells

Lin, Yu-Fen (University of Texas Southwestern)
Chen, Banjamin P. (University of Texas Southwestern)
Li, Wende (Massachusetts General Hospital/Harvard Medical School)
Perko, Z. (TU Delft RST/Reactor Physics and Nuclear Materials)
Wang, Yi (Massachusetts General Hospital/Harvard Medical School)
Testa, Mauro (Massachusetts General Hospital/Harvard Medical School)
Robert, Schneider (Massachusetts General Hospital/Harvard Medical School)
Lu, Hsaio-Ming (Massachusetts General Hospital/Harvard Medical School)
Gerweck, Leo E. (Massachusetts General Hospital/Harvard Medical School)

2018-01

Purpose: Variations in the radiosensitivity of tumor cells within and between tumors impact tumor response to radiation, including the dose required to achieve permanent local tumor control. The increased expression of DNA-PKcs, a key component of a major DNA damage repair pathway in tumors treated by radiation, suggests that DNA-PKcs– dependent repair is likely a cause of tumor cell radioresistance. This study evaluates the relative biological effect of spread-out Bragg-peak protons in DNA-PKcs–deficient cells and the same cells transfected with a functional DNA-PKcs gene. Materials and Methods: A cloned radiation-sensitive DNA-PKcs–deficient tumor line and its DNA-PKcs–transfected resistant counterpart were used in this study. The
presence of functional DNA-PKcs was evaluated by DNA-PKcs autophosphorylation.
Cells to be proton irradiated or x-irradiated were obtained from the same single cell suspension and dilution series to maximize precision. Cells were concurrently exposed to 6-MV x-rays or mid 137-MeV spread-out Bragg peak protons and cultured for colony formation. Results: The surviving fraction data were well fit by the linear-quadratic model for each of 8 survival curves. The results suggest that the relative biological effectiveness of mid spread-out Bragg peak protons is approximately 6% higher in DNA-PKcs–mediated resistant tumor cells than in their DNA-PKcs–deficient and radiation-sensitive counterpart.
Conclusion: DNA-PKcs–dependent repair of radiation damage is less capable of
repairing mid spread-out Bragg peak proton lesions than photon-induced lesions, suggesting protons may be more efficient at sterilizing DNA-PKcs–expressing cells that are enriched in tumors treated by conventional fractionated dose x-irradiation.

http://resolver.tudelft.nl/uuid:1d801d23-69ae-489f-989e-7cc131a08067

https://doi.org/10.14338/IJPT-17-00025.1

2331-5180

The International Journal of Particle Therapy, 33-39

Institutional Repository

journal article

© 2018 Yu-Fen Lin, Banjamin P. Chen, Wende Li, Z. Perko, Yi Wang, Mauro Testa, Schneider Robert, Hsaio-Ming Lu, Leo E. Gerweck