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PURPOSE We assessed whether adding sodium borocaptate (BSH) or 4-borono-L-phenylalanine (BPA) to cells irradiated with proton beams influenced the biological effectiveness of those beams against prostate cancer cells to investigate if the alpha particles generated through proton-boron nuclear reactions would be sufficient to enhance the biological effectiveness of the proton beams. METHODS We measured clonogenic survival in DU145 cells treated with 80.4 ppm BSH or 86.9 ppm BPA, or their respective vehicles, after irradiation with 6 MV x-rays, 1.2 keV/μm (low linear-energy-transfer [LET]) protons, or 9.9 keV/μm (high-LET) protons. We also measured γH2AX and 53BP1 foci in treated cells at 1 h and 24 h after irradiation with the same conditions. RESULTS We found that BSH radiosensitized DU145 cells across all radiation types. However, no difference was found in relative radiosensitization, characterized by the sensitization enhancement ratio (SER) or the relative biological effectiveness (RBE), for vehicle-treated versus BSH-treated cells. No differences were found in numbers of γH2AX or 53BP1 foci or γH2AX/53BP1 colocalized foci for vehicle-treated versus BSH-treated cells across radiation types. BPA did not radiosensitize DU145 cells nor induce any significant differences when comparing vehicle- versus BPA-treated cells for clonogenic cell survival or γH2AX and 53BP1 foci or γH2AX/53BP1 colocalized foci. CONCLUSIONS Treatment with 11 B, at concentrations of 80.4 ppm from BSH or 86.9 ppm from BPA, had no effect on the biological effectiveness of proton beams in DU145 prostate cancer cells. Our results agree with published theoretical calculations indicating that the contribution of alpha particles from such reactions to the total absorbed dose and biological effectiveness is negligible. We also found that BSH radiosensitized DU145 cells to x-rays, low-LET protons, and high-LET protons but that the radiosensitization was not related to DNA damage. This article is protected by copyright. All rights reserved.