Many of the mutagenic or lethal effects of ionizing radiation can be traced to structural and chemical modification of cellular DNA through double-strand breaks (DSB) and clustered lesions. Although the development of mechanistic models of radiation damage in DNA has reached a high level of sophistication, further refinements are needed to understand fully the underlying mechanisms in particular on a molecular level. The proposed studies are designed to provide, in a comprehensive manner, missing information about the molecular pathways that lead from initial deposition of radiative energy to the formation of double strand breaks and lesions in DNA.
The genotoxic effects of ionising radiation (a, b, g, ions) in living cells are produced not only by the direct impact of the primary high energy projectiles but are also induced by secondary species generated by the primary ionising radiation. For example it has recently been suggested that localization of low energy electrons on the nucleotide bases through the formation of short lived anions leads to molecular dissociation and thence to single and double strand breaks in the DNA. Thus radiation damage may be described/understood at an individual molecule level. This also introduces the exciting prospect that it may be possible to eventually manipulate the effects of ionizing radiation at a molecular level within the cell. For example such a molecular picture may be used to explain the well known correlation between electron attachment rates of many molecules and their carcinogenicity and may be used to suggest new compounds to be adopted in radiation therapy as treatment enhancing sensitizers.
Hence the simultaneous and consecutive action of the primary, secondary and tertiary species (including also radicals such as H and OH formed by the destruction of the water molecules surrounding the DNA and in other chemical reactions) have to be included in any quantitative consideration about radiation damage. Such a research programme requires an interdisciplinary approach constructed around a core programme of experimental studies of the interaction of photons, protons, ions and electrons with bio-molecular systems. This COST Action will concentrate on the effects of primary radiation (protons, highly charged ions and photons) as well as reactions of secondary electrons. These studies will be performed using several selected prototypical bio-molecules as targets. These studies will therefore be performed on simple molecules (e.g. H2O and DNA bases) as well as on more complex bio-molecules such as nucleotides and plasmid DNA. In addition to bridge the existing gap between studies in the gas phase and the condensed phases (solid, liquid) investigations of the radiation action on mixed clusters consisting of bio-molecules and water and on surface deposited bio-molecules will be performed in order to explore the complex situation in the natural environment.
The very recent development, refinement and application of new experimental techniques (e.g. novel types of beam sources, multi-coincidence detection techniques, high resolution beam and mass and energy spectrometry techniques, sophisticated drift tube techniques) makes this the ideal time for carrying out an ambitious and coordinated series of experiments planned to attack the many open questions in this field. The concentration of research teams with the wide range of necessary complementary experimental methods and joint expertise and interest in the field of radiation damage in bio-molecules is presently unique to Europe and ideal for exploiting this potential. In addition, the experimental groups will be supported by the theoretical expertise of leading groups in the area of quantum chemical description of collisions providing the basis for a major advance in the understanding and theoretical treatments (simulation) of the action of the abundant low-energy depositions that occur around the tracks of all types of radiation in large complex systems. The purpose of this COST Proposal is to facilitate such a research programme through the co-ordination of the research of leading international research groups. Links with some existing EU funded ‘Networks’ will be established and the programme may also form the core of a Network of Excellence to be submitted as part of the forthcoming EU Framework VI programme. It is interesting to note in this context, that the work planned in this project is of direct use and likely to provide important basic physical input information for other EU-EURATOM projects in radiation sciences. Indeed these activities, in turn, are supervised – on request of the EU – by the scientific network EULEP (European Late Effect Project) with whom some of the proposed COST Action participants (see Additional information) are already participants.