Journal
JOURNAL OF RADIATION RESEARCH AND APPLIED SCIENCES
Volume 14, Issue 1, Pages 260-270Publisher
ELSEVIER
DOI: 10.1080/16878507.2021.1949675
Keywords
Proton irradiation; handrontherapy; transcriptome modulation; mouse skin; spectroscopy FTIR microspectroscopy
Funding
- European Community Horizon 2020 research and innovation program [730872]
- National Institute of Nuclear Physics (INFN)
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The study investigates the potential impact and diffusion extent of proton beam therapy on surrounding tissues, using transcriptome analysis of biomarker genes and assessment of lipid alterations. Evidence of transcriptional modulation at considerable distance from the beam's target is shown, indicating a possible diffusion of regulatory molecules from high dose irradiated cells to distant tissues.
Hadron therapy by proton beams represents an advanced anti-cancer strategy due to its highly localized dose deposition allowing a greater sparing of normal tissue and/or organs at risk compared to photon/electron radiotherapy. However, it is not clear to what extent non-targeted effects such as transcriptional modulations produced along the beamline may diffuse and impact the surrounding tissue. In this work, we analyze the transcriptome of proton-irradiated mouse skin and choose two biomarker genes to trace their modulation at different distances from the beam's target and at different doses and times from irradiation to understand to what extent and how far it may propagate, using RNA-Seq and quantitative RT-PCR. In parallel, assessment of lipids alteration is performed by FTIR spectroscopy as a measure of tissue damage. Despite the observed high individual variability of expression, we can show evidence of transcriptional modulation of two biomarker genes at considerable distance from the beam's target where a simulation system predicts a significantly lower adsorbed dose. The results are compatible with a model involving diffusion of transcripts or regulatory molecules from high dose irradiated cells to distant tissue's portions adsorbing a much lower fraction of radiation.
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