Attachment 7 Research on the Biological Effect of Heavy Charged Particles with Different Energies For over 50 years biological experiments have been held at charged particle accelerators in the Joint Institute for Nuclear Research (JINR). The start of the research was connected with the exploration of the near-Earth space environment and provision of radiation safety for Man in the outer space. This kind of research was aimed at the studies of the biological action produced by different types of space radiation and, primarily, by high energy protons. When first space flights with animals and man were prepared it was not clear how living organisms would behave in the conditions of the multi-component radiation action, including that of high energy protons which are generated by the Sun and come from the depth of the Galaxy. It became possible to solve this task in the ground conditions, irradiating biological objects at the first accelerator of Dubna that generated high energy proton beams. At the initiative and support of Academicians A.V. Lebedinsky, V.V. Parin, O.G. Gazenko, extensive experiments were started at JINR to determine biological efficiency of high energy protons, and these studies made it possible to provide radiation protection for the crews in the first space flights. Thus, Dubna has made a weighty contribution to the exploration of the near-Earth space environment. Subsequently, radiobiologists of JINR, in collaboration with specialists from our country and other member states of the Institute, continued these studies. In 1978, the Sector for biological research was established; it conducted research in fundamental issues of general and space radiobiology: its aims were to study the mechanisms that specify the distinctions in biological efficiency of ionizing radiation with different physical characteristics, to investigate fundamental processes that lie at the root of the mutagenic action produced by accelerated charged particles of high energy. Since 2005 this research has been conducted at the Laboratory of Radiation Biology – a new JINR division that overlapped studies of biological action of ionizing radiation and radiation protection. At present, research is conducted at JINR for the multipurpose studies of regularities and mechanisms of the action produced by heavy charged particles on the molecular, cell, tissue and organism levels of the biological organization. Studies are continued of the formation peculiarities of cluster DNA double-strand breaks – the most severe damage in genetic structures at the action of heavy charged particles. As it is known, these types of damage lie at the root of the cell death, formation of various mutations, cell malignant transformations. Research is conducted of the action of the low-dose radiation types on the cell level. The studies in the field of radiation physiology are of particular interest, as they are concerned with the issues of the influence cast by heavy charged particles on the eye retina, the structure and functions of the central nervous system. These elaborations are exclusively urgent for the solution of tasks in space radiobiology. The recently obtained data on the development of radiation syndromes at the action of heavy charged particles on the brain structures that lead to its integrity breach afford ground to regard the central nervous system as a “critical” one in evaluating the risk of radiation action on the space crewmembers’ organisms in interplanetary flights. The topics of such research are quite new. Many responses of the central nervous system to the radiation influence, both on the cell and organism levels, still remain unexplored. At the present time, scientists of the Laboratory of Radiation Biology together with specialists from 1 other Russian institutions hold multipurpose research aimed at the studies of the central nervous system response to the action of ionizing radiation. A series of experiments have been held so far at the Dubna accelerators of heavy nuclei to investigate separate neurochemical mechanisms that may be at the heart of changes in behaviour and memory impairment that are observed in small laboratory animals in early and long term periods of time after irradiation. The report “Early and long-term effects of low- and high-LET radiation on the rat behavior and the monoamine metabolism in different brain regions” (Belov et al.) that was registered for presentation at the 40th Scientific Assembly of COSPAR will discuss the topic. The studies conducted at Dubna ought to give information on the issue how dangerous is the influence caused by heavy nuclei of the galactic cosmic radiation in any interplanetary, including the one to Mars, mission. It is vital to find the answer to the question if impairments in supreme integrative functions of the central nervous system will occur at the action of such a unique radiation factor as heavy charged particles, whose character of energy transfer differs drastically from the usual types of ionizing radiation (X-rays and gamma-rays). It is necessary to find out to what extent these impairments will grow at the dramatic psychological strain that inevitably will occur in the interplanetary flight. In this context, the experiments with primates are important, as they allow the evaluation of mainly behavioural and cognitive reactions that occur in different periods of time after exposure to heavy charged particles. First experiments of this type are already under way in Dubna, using carbon nuclei and protons of high energy. Such research is an important period of extrapolation of the changes observed in laboratory animals onto Man. One of the concluding results of the whole complex of scientific studies at the Laboratory of Radiation Biology of JINR must be in the facts that make it possible for us to approach the estimation of the risk in radiation action in the conditions of an interplanetary flight. The risk concept used today of the nearest radiation-induced effects that can occur during the mission considers mainly the impairment of the bone-marrow hemopoiesis, damage to skin and other organs and tissues of the organism. The long-term effects of irradiation that can form during the subsequent life period are traditionally related to the growth of tumour processes in the organism. However, facts have been obtained that allow us to presume that the total radiation risk for space crewmembers that is evaluated with an account for the growth of impairments in other systems (the central nervous system, the vision system, the cardiovascular system, the neuroendocrinal system, etc.) is several times bigger, in comparison with the progression of tumour diseases. Thus, the research in this field will promote development of a principally new concept of risk for crews of spaceships that will have in its basis the notion of probability for successful accomplishment of the mission and possible formation of radiation damage, including that in the physiological systems that have not be considered earlier in estimation of radiation hazards during the mission. 2