Heterogeneity in biological response of MDA-MB-231 cells after proton irradiation along different parts of the depth-dose curve: before, within, and behind the Bragg peak.

Background: Proton therapy has garnered attention as an advanced radiation treatment modality for breast cancer due to its ability to deliver highly precise doses to the target area while minimizing exposure to surrounding healthy tissues. The aim was to detect potential variations in radiobiological response along different parts of the proton depth-dose curve. Materials and methods: MDA-MB-231 cells were specifically irradiated before, within, and beyond the Bragg peak with a 5 Gy dose, with photons used as a reference. The radiobiological response was evaluated using clonogenic assays, relative γH2AX levels, and quantitative polymerase chain reaction (qPCR) analysis of DNA damage response genes. Results: A trend of increasing magnitude in radiobiological response was observed with increasing depth of cell irradiation, accompanied by a decrease in survival fraction. Furthermore, differences were noted, particularly in γH2AX levels along the Bragg peak, with higher values of DNA double-strand breaks (DNA DSB) observed at the end of the depth-dose curve. Conclusions: These findings suggest that despite administering a consistent proton dose to the target area, there can be a range of different biological reactions, which might have significant indications for clinical procedures.