TY  - JOUR
AU  - Mladenov, Emil
AU  - Pressler, Mina
AU  - Mladenova, Veronika
AU  - Soni, Aashish
AU  - Li, Fanghua
AU  - Heinzelmann, Feline
AU  - Esser, Johannes Niklas
AU  - Hessenow, Razan
AU  - Gkika, Eleni
AU  - Jendrossek, Verena
AU  - Timmermann, Beate
AU  - Stuschke, Martin
AU  - Iliakis, George
TI  - Evidence for Quasi-High-LET Biological Effects in Clinical Proton Beams That Suppress c-NHEJ and Enhance HR and Alt-EJ.
JO  - Cells
VL  - 15
IS  - 1
SN  - 2073-4409
CY  - Basel
PB  - MDPI
M1  - DKFZ-2026-00082
SP  - 86
PY  - 2026
N1  - #DKTKZFB26#
AB  - Protons are conventionally regarded as a low-linear energy transfer (low-LET) radiation modality with a relative biological effectiveness (RBE) of 1.1, suggesting direct mechanistic similarity to X-rays in the underpinning biological effects. However, exposure to spread-out Bragg peak (SOBP) protons reveals instructive deviations from this assumption. Indeed, proton beams have a maximum LET of  5 keV/µm but display reduced reliance on classical non-homologous end joining (c-NHEJ) as well as an increased dependence on homologous recombination (HR) and alternative end joining (alt-EJ). These features are well described in cells exposed to high-LET radiation and typically manifest between 100 and 150 keV/µm. We hypothesized that this apparent discrepancy reflects biological consequences of proton-beam properties that remain uncharacterized. In the present study, we outline exploratory experiments aiming at uncovering such mechanisms. We begin by investigating for both entrance and SOBP protons the dose-dependent engagement of HR we recently showed for X-rays. Consistent with our previous findings with X-rays, HR engagement after exposure to both types of proton beams declined with dose, from  80
KW  - Linear Energy Transfer
KW  - Humans
KW  - DNA End-Joining Repair: radiation effects
KW  - Protons
KW  - Homologous Recombination: radiation effects
KW  - Proton Therapy
KW  - Dose-Response Relationship, Radiation
KW  - X-Rays
KW  - DNA double strand breaks (DSBs) (Other)
KW  - alternative end joining (alt-EJ) (Other)
KW  - classical non-homologous end joining (c-NHEJ) (Other)
KW  - homologous recombination (HR) (Other)
KW  - ionizing radiation (IR) (Other)
KW  - linear energy transfer (LET) (Other)
KW  - proton radiation (Other)
KW  - relative biological effectiveness (RBE) (Other)
KW  - structural chromosomal abnormalities (SCAs) (Other)
KW  - Protons (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41511369
C2  - pmc:PMC12785619
DO  - DOI:10.3390/cells15010086
UR  - https://inrepo02.dkfz.de/record/307610
ER  -