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

Abstract

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.

Comparative Cytogenetic Abnormalities in Paired Choroidal Melanoma Samples Obtained Before and After Proton Beam Irradiation by Transscleral Fine-Needle Aspiration Biopsy and Endoresection

“…Given the timing of sampling with respect to irradiation, two phenomena may account for these modifications: either radiation-induced DNA modifications or tumor cellular heterogeneity. Proton particles irradiation result in multiple single and double strand breaks, randomly disseminated over all 46 chromosomes, as ascertained by experimental [29,30] and simulation models [31,32]. DNA modifications between pre- and post-irradiation samples showed a preferential location on certain chromosomes (notably 3, 8q, 6, and 4), and consisted often in additions or deletions of large chromosome segments, not only focal breaks, arguing against a consequence of proton beam irradiation.…”

Analysis of the Dose Drop at the Edge of the Target Area in Heavy Ion Radiotherapy

“…Beam delivery is the process of transporting heavy ion beam from accelerator to target area for irradiation therapy. During the active beam delivery, the accelerator actively changes the energy of the particles to change the incidence depth of the ion beam [ 12 ]. Meanwhile, the magnetic scanning system is used to guide the pencil beam to carry out conformal or intensity-modulated irradiation therapy on the tumor target region.…”