Charged particle effects: Experimental and theoretical studies on the mechanisms underlying the induction of molecular and cellular damage and the modulation of intercellular signalling

Alloni, D. and Antonelli, F. and Ballarini, F. and Belli, M. and Bertolotti, A. and Campa, A. and Dini, V. and D'Ercole, L. and Esposito, G. and Facoetti, A. and Friedland, W. and Giovannini, C. and Grande, S. and Guidoni, L. and Liotta, M. and Lisciandro, F. and Luciani, A. M. and Mantovani, L. and Mariotti, L. and Molinelli, S. and Nano, R. and Ottolenghi, Andrea and Palma, A. and Paretzke, H. G. and Pasi, F. and Raffaele, L. and Rosi, A. and Sapora, O. and Scannicchio, D. and Simone, G. and Sorrentino, E. and Tabocchini, M. A. and Viti, V. (2008) Charged particle effects: Experimental and theoretical studies on the mechanisms underlying the induction of molecular and cellular damage and the modulation of intercellular signalling. Il nuovo cimento C, 31 (1). pp. 21-38. ISSN 1826-9885

[img]
Preview
Text
ncc9282.pdf - Published Version

Download (957kB) | Preview
Official URL: https://www.sif.it/riviste/sif/ncc/econtents/2008/...

Abstract

In this paper we present the main outcomes of a wide collaborative effort (carried out within the INFN project “EPICA” and in part within the European projects “RISC-RAD” and “NOTE” and the ASI project MoMa-COUNT), both experimental and theoretical, devoted to the characterization and quantification of the induction of DNA-targeted and non-DNA-targeted molecular and cellular biological endpoints, following irradiation of human cells with different charged particles. The work was mainly aimed at reaching a better understanding of the mechanisms governing the physical and biophysical pathways leading from the initial energy deposition by radiation in matter to the induction of observable radiobiological damage, with particular focus on the role played by radiation quality. More specifically, we characterized the induction of DNA DSB within different fragment-size ranges outlining the effectiveness of high-LET radiation at inducing small fragments and thus clustered DNA breaks, which can evolve in terms of endpoints like chromosome aberrations (CAs). This was confirmed by the development and application of a model of CA induction based on the assumption that only clustered DNA breaks can lead to aberrations. Concerning non-DNA-targeted damage, we quantified the time-dependent induction of medium-mediated DNA damage in bystander cells and we characterized the time and dose dependence of cytokine concentration in the culture medium of sham-irradiated and irradiated cells, since medium-mediated bystander damage is thought to arise from molecular signalling between irradiated and unirradiated cells. The mechanisms governing such signalling were investigated developing a model and a MC code simulating cytokine release, diffusion and internalization, showing good agreement with experimental data. Non-DNA-targeted effects were further characterized by MRS investigation of the radiation effects on lipids and oxidative metabolism, which are particularly relevant also considering that they may be differently expressed in different tumors and in normal tissues.

Item Type: Article
Uncontrolled Keywords: Effects of ionizing radiation on biological systems
Subjects: 500 Scienze naturali e Matematica > 530 Fisica
Depositing User: Marina Spanti
Date Deposited: 23 Mar 2020 14:44
Last Modified: 23 Mar 2020 14:44
URI: http://eprints.bice.rm.cnr.it/id/eprint/16328

Actions (login required)

View Item View Item