Fluorescence In Situ Hybridization-Based Chromosome Aberration Analysis Unveils the Mechanistic Basis for Boron-Neutron Capture Therapy’s Radiobiological Effectiveness

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 main...

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Published inApplied sciences Vol. 14; no. 3; p. 1171
Main Authors Elia, Valerio Cosimo, Fede, Francesca, Bortolussi, Silva, Cansolino, Laura, Ferrari, Cinzia, Formicola, Emilia, Postuma, Ian, Manti, Lorenzo
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 01.01.2024
Subjects
BNCT
Boron
BPA
Cancer therapies
Cell death
chromosome aberration
Chromosomes
Clinical trials
complex DNA damage
DNA damage
Dosimetry
FISH techniques
Fluorescence
high-LET radiation
Neutrons
Pediatrics
Radiation therapy
Tumors
X-rays
Germany
Italy
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Summary: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.
ISSN:2076-3417
2076-3417
DOI:10.3390/app14031171