Purpose
DNA damage mechanism of proton beams may differ at different depths in water or human body. This study was to clarify the difference in production of DNA base damage at two different lineal-energy points of proton beams. In addition, the effect of radical scavenger edaravone was tested whether it can relatively enhance the direct effect at Bragg peak while suppressing the indirect effect at plateau region of proton beams.
Methods
ST-DNA solution and MOLT4 cells were irradiated with 200 MeV proton beams at two different lineal-energy points, i.e., at plateau and at Bragg peak. 200 kV X-rays were used for comparison. Immediately after each irradiation with or without edaravone, ST-DNA solution had been frozen and kept until 8-OHdG was extracted and quantified by HPLC. Using MOLT4 cells, DNA double strand breaks at two lineal-energy points were visualized by immunohistochemical staining of gamma-H2AX foci which were sequentially quantified by image processing.
Results
Production of 8-OHdG in ST-DNA solution was significantly higher after irradiation with X-rays than proton beams of both lineal-energy points. Furthermore, it was higher at plateau than at Bragg peak of proton beams. Edaravone suppressed production of 8-OHdG after every irradiation, and this effect was greater in irradiation with proton beams at plateau than at Bragg peak. Although there was no remarkable difference in gamma-H2AX focus formation after irradiation with proton beams at plateau and Bragg peak, addition of edaravone significantly reduced the focus formation at plateau of proton beams while no significant effect was observed at Bragg peak.
Conclusions
It was demonstrated that the indirect effect measured by 8-OHdG production was relatively higher at plateau region as compared to that at Bragg peak of proton beams. This may indicate that use of edaravone can protect the normal tissue at the plateau region while preserving the direct tumor killing effect at Bragg peak of proton beams.