Boron-Neutron Capture Therapy (BNCT) is a tumor-selective radiotherapy, based on the nuclear capture reaction ¹⁰B(n,α)⁷Li producing short range α-particles and recoiling ⁷Li nuclei exclusively confined to boron-enriched cancer cells. These particles possess high Linear Energy Transfer (LET) and mainly generate clustered DNA strand breaks, which are less faithfully restored by intracellular repair. Mis-rejoined breaks yield chromosome aberrations (CAs), which, for high-LET radiation, are more complex in nature than after sparsely ionizing photons/electrons used in conventional radiotherapy, which leads to increased cell-killing ability. However, such a radiobiological tenet of BNCT has been scantily studied at the DNA level. Therefore, the aim of this work was to evaluate CAs induced by BNCT in comparison to X-rays in genomically stable normal human epithelial mammary MCF10A cells. Two Fluorescence In Situ Hybridization (FISH)-based techniques were applied to calyculin A-induced prematurely condensed chromosomes: Whole Chromosome Painting and multicolor(m)-FISH. Not only did BNCT induce a greater CA frequency than X-ray irradiation, but m-FISH karyotype-wide analysis confirmed that CAs following BNCT exhibited a much higher degree of complexity compared to X-rays. To our knowledge, this is the first time that such evidence supporting the radiobiological superiority of BNCT has been shown.

Objective. This study aims to perform a comprehensive microdosimetric characterization of a clinical helium ion beam at the Heidelberg ion-beam Therapy center, assessing radiation quality along a spread-out Bragg peak (SOBP) and providing experimental data to support the biological effectiveness of helium ions in clinical applications. Approach. Microdosimetric spectra were measured at several water depths within the SOBP using two solid-state detectors: a silicon and a synthetic single-crystal diamond detector. Microdosimetric quantities, including dose-mean lineal energy ( y D ) and frequency-mean lineal energy ( y F ), were derived. Monte Carlo simulations with the Geant4 toolkit replicated the experimental setup to validate the measured quantities. The modified microdosimetric kinetic model was also applied to estimate the relative biological effectiveness at 10% survival (RBE₁₀). SAOS-2 and U2OS clonogenic assays were performed under identical irradiation conditions at the same facility to benchmark the RBE predictions. Main results. The experimental results demonstrated a progressive increase in y D values along the beam path, peaking at the distal edge of the SOBP, consistent with the simulated dose-averaged linear energy transfer distribution. The RBE₁₀ values estimated by the two solid-state detectors showed good agreement with the experimental data from clonogenic assays, within the associated uncertainties. Significance. These findings underscore the utility of advanced solid-state detectors for helium beam characterization and highlight the importance of microdosimetry in improving radiobiological modeling. The results provide further evidence supporting the clinical potential of helium ion therapy, particularly for tumors requiring high precision and maximal healthy tissue sparing.

Proton beam therapy is considered a step forward with respect to electromagnetic radiation, thanks to the reduction in the dose delivered. Among unwanted effects to healthy tissue, cardiovascular complications are a known long-term radiotherapy complication. The transcriptional response of cardiac tissue from xenografted BALB/c nude mice obtained at 3 and 10 days after proton irradiation covering both the tumor region and the underlying healthy tissue was analyzed as a function of dose and time. Three doses were used: 2 Gy, 6 Gy, and 9 Gy. The intermediate dose had caused the greatest impact at 3 days after irradiation: at 2 Gy, 219 genes were differently expressed, many of them represented by zinc finger proteins; at 6 Gy, there were 1109, with a predominance of genes involved in energy metabolism and responses to stimuli; and at 9 Gy, there were 105, mainly represented by zinc finger proteins and molecules involved in the regulation of cardiac function. After 10 days, no significant effects were detected, suggesting that cellular repair mechanisms had defused the potential alterations in gene expression. The nonlinear dose–response curve indicates a need to update the models built on photons to improve accuracy in health risk prediction. Our data also suggest a possible role for zinc finger protein genes as markers of proton therapy efficacy.

The fruits of Solanum lycopersicum L. cultivar “Microtom” are a powerful source of antioxidants. We investigated whether two light-quality regimes, i.e., fluorescent white (FL) and red-blue (RB), influenced the antioxidant composition in such fruits, and assessed the potential radioprotective properties of their extracts on normal human cells exposed to clinical photons as used in cancer radiotherapy (RT). Increasing normal-tissue tolerance to radiation is critical for reducing the risk of RT-associated sequelae. Biochemical characterization showed that RB enhanced the content of antioxidant phytochemicals (i.e., polyphenols, flavonoids, total carotenoids, lycopene) while FL promoted ascorbic acid synthesis. Initially tested at 200 µg ml-1, RB-derived extracts decreased radiation-induced DNA damage as measured by the cytokinesis-block micronucleus (CBMN) assay in epidermal HaCaT cells. Both RB and FL regimes were subsequently studied in MCF-10A breast cancer (BC) cells, a model of normal-tissue radioresponse in BC RT, using extracts at 100 and 200 µg ml-1 also evaluating oxidative stress by a ROS detection assay. Both FL and RB afforded radioprotection. However, RB suppressed radiation-induced MN formation and oxidative stress to a greater extent compared to FL. Therefore, modulation of light-quality regimes represents an innovative approach for developing radionutraceuticals with potential benefits for RT patients.

The fruits of Solanum lycopersicum L. cultivar “Microtom” are a powerful source of antioxidants. We investigated whether two light-quality regimes, i.e., fluorescent white (FL) and red-blue (RB), influenced the antioxidant composition in such fruits, and assessed the potential radioprotective properties of their extracts on normal human cells exposed to clinical photons as used in cancer radiotherapy (RT). Increasing normal-tissue tolerance to radiation is critical for reducing the risk of RT-associated sequelae. Biochemical characterization showed that RB enhanced the content of antioxidant phytochemicals (i.e., polyphenols, flavonoids, total carotenoids, lycopene), while FL promoted ascorbic acid synthesis. Initially tested at 200 µg/mL, RB-derived extracts decreased radiation-induced DNA damage as measured by the cytokinesis-block micronucleus (CBMN) assay in epidermal HaCaT cells. Both RB and FL regimes were subsequently studied in MCF-10A breast cancer (BC) cells, a model of normal-tissue radioresponse in BC RT, using extracts at 100 and 200 µg/mL and also evaluating oxidative stress by a ROS detection assay. Both FL and RB afforded radioprotection. However, RB suppressed radiation-induced MN formation and oxidative stress to a greater extent compared to FL. Therefore, modulation of light-quality regimes represents an innovative approach for developing radionutraceuticals with potential benefits for RT patients.