Clustered DNA Double-Strand Breaks and Neuroradiobiological Effects of Accelerated Charged Particles

Abstract

The irradiation of brain structures with accelerated heavy charged particles during interplanetary flights or brain tumor therapy raises a number of questions regarding possible neurophysiological disorders in the central nervous system (CNS). Hardly repairable clustered DNA double-strand breaks apparently can have significant influence on the specifics of the development of radiation syndromes in the CNS after heavy charged particle exposure. The mechanisms of these disorders still remain unclear. Taking this into account, we have used immune cyto- and histochemistry techniques to study regularities of the formation of radiationinduced foci in human cell DNA in vitro and in rodent brain neurons in vivo after exposure to charged particles of different energies. It has been found that heavy charged particles induce clustered DNA damage in the genome of proliferating (human fibroblasts) and non-proliferating (Purkinje neurons) cells. We have suggested that changes in genetic structures can affect the conformation of the key proteins participating in neurophysiological processes and violate the normal functioning of the synaptic receptors. As an example, we have considered the action of double point mutations in the gene sequence encoding the proteins of the glutamate receptor NMDA. Using computer molecular dynamics techniques, we have revealed a twofold change in the conductance of the receptor’s ion channel, which incorporates mutant forms of the protein subunits NR2.