Abstract
Purpose: It is desirable to establish a robust combined physical-biological system for evaluation of biological effects of high energy proton beams (PB). This study was to clarify whether a system composed of measurement of y* values and measurement of DNA base damages and DNA double strand breaks (DDSB) production is useful for this purpose or not. In addition, the effect of radical scavenger edaravone was tested in this system.
Methods: ST-DNA solution and MOLT4 cells were irradiated with 155 MeV PB at two different y* points, i.e., at plateau (P) and Bragg peak (B). After each irradiation with or without edaravone, ST-DNA solution was extracted to 8-OHdG and quantified by HPLC. DDSB were evaluated by agarose gel electrophoresis after each irradiation. In addition, MOLT4 cells irradiated at the two y* points were visualized by immunohistochemical staining for gamma-H2AX foci detection.
Results: Production of 8-OHdG in ST-DNA solution was significantly higher at plateau (P) than Bragg peak (B). DDSB was higher at B than at P in agarose gel electrophoresis. Edaravone reduced production of 8-OHdG after every irradiation. There was no remarkable difference in gamma-H2AX focus formation in MOLT4 at P and B points, however, edaravone suppressed production of foci at P point.
Conclusions:
For the standardization of PBT, unification of proton microdosimetry and biological evaluation at robust endpoints are mandatory. It was demonstrated that a combination of lineal energy (y*) measurement, and DNA base-damage and DDSB measurements could be a good candidate of such evaluation systems.
