Title
In silico nanodosimetry: new insights into nontargeted biological responses to radiation.
Abstract
The long-held view that radiation-induced biological damage must be initiated in the cell nucleus, either on or near DNA itself, is being confronted by mounting evidence to suggest otherwise. While the efficacy of cell death may be determined by radiation damage to nuclear DNA, a plethora of less deterministic biological responses has been observed when DNA is not targeted. These so-called nontargeted responses cannot be understood in the framework of DNA-centric radiobiological models; what is needed are new physically motivated models that address the damage-sensing signalling pathways triggered by the production of reactive free radicals. To this end, we have conducted a series of in silico experiments aimed at elucidating the underlying physical processes responsible for nontargeted biological responses to radiation. Our simulation studies implement new results on very low-energy electromagnetic interactions in liquid water (applicable down to nanoscales) and we also consider a realistic simulation of extranuclear microbeam irradiation of a cell. Our results support the idea that organelles with important functional roles, such as mitochondria and lysosomes, as well as membranes, are viable targets for ionizations and excitations, and their chemical composition and density are critical to determining the free radical yield and ensuing biological responses.
Year
DOI
Venue
2012
10.1155/2012/147252
COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE
Keywords
Field
DocType
dna damage,photons,protons,electrons,mutagenesis,signal transduction,cytoplasm,radiation,computer simulation,mitochondria,biological,nanotechnology,cell death,dna,water,radiobiology,ions,free radicals,insights
Biology,Cell,DNA damage,Signal transduction,Artificial intelligence,In silico,Nanotechnology,Nuclear DNA,Biophysics,Cytoplasm,Mutagenesis,Radiobiology,Machine learning
Journal
Volume
ISSN
Citations 
2012
1748-670X
0
PageRank 
References 
Authors
0.34
0
6
Name
Order
Citations
PageRank
Zdenka Kuncic101.01
Hilary L Byrne200.34
Aimee L McNamara300.34
S. Guatelli432.36
Westa Domanova500.34
Sébastien Incerti611.09