Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, Texas, USA.
Med Phys. 2022 Sep;49(9):6098-6109. doi: 10.1002/mp.15824. Epub 2022 Jul 6.
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.
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 and 24 h after irradiation with the same conditions.
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 or the relative biological effectiveness, for vehicle- versus BSH-treated cells. No differences were found in numbers of γH2AX or 53BP1 foci or γH2AX/53BP1 colocalized foci for vehicle- versus BSH-treated cells across radiation types. BPA did not radiosensitize DU145 cells nor induced any significant differences when comparing vehicle- versus BPA-treated cells for clonogenic cell survival or γH2AX and 53BP1 foci or γH2AX/53BP1 colocalized foci.
Treatment with 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.
我们评估了在质子束照射下向细胞中添加硼替佐米（BSH）或 4-硼代苯丙氨酸（BPA）是否会影响这些射线对前列腺癌细胞的生物学效应，以研究质子-硼核反应产生的α粒子是否足以增强质子射线的生物学效应。
我们测量了用 80.4ppm 的 BSH 或 86.9ppm 的 BPA 或其相应载体处理后的 DU145 细胞在接受 6MV X 射线、1.2keV/μm（低线性能量传递[LET]）质子或 9.9keV/μm（高 LET）质子照射后的集落存活情况。我们还测量了在相同条件下照射后 1 小时和 24 小时时处理细胞中的 γH2AX 和 53BP1 焦点。
我们发现 BSH 使 DU145 细胞对所有辐射类型均具有放射增敏作用。然而，在载体与 BSH 处理细胞的相对放射增敏作用（以增敏增强比或相对生物效应来表示）方面，没有发现差异。在不同的辐射类型中，载体与 BSH 处理细胞之间的 γH2AX 或 53BP1 焦点或 γH2AX/53BP1 共定位焦点的数量没有差异。BPA 既没有使 DU145 细胞放射增敏，也没有在比较载体与 BPA 处理细胞的集落存活或 γH2AX 和 53BP1 焦点或 γH2AX/53BP1 共定位焦点时产生任何显著差异。
用 80.4ppm 的 BSH 或 86.9ppm 的 BPA 处理 DU145 前列腺癌细胞时，BSH 的浓度对质子束的生物学效应没有影响。我们的结果与已发表的理论计算结果一致，表明这种反应产生的α粒子对总吸收剂量和生物学效应的贡献可以忽略不计。我们还发现，BSH 使 DU145 细胞对 X 射线、低 LET 质子和高 LET 质子产生放射增敏作用，但这种放射增敏作用与 DNA 损伤无关。
