Report on Activities of COST action P9
RADAM 2005-6

Scientific Progress

A full scientific review is in preparation for the Final MC meeting to be held in RADAM07 in Dublin. A brief review/update is therefore given here

WG1 Some of the most dramatic progress in the course of the Action has been in the study of electron scattering from bio-molecules in particular the DNA bases adenine, cytosine, guanine, thymine and RNA base uracil and most recently the larger biomolecules including glycine, simple sugars and acids. The University of Innsbruck (UIBK) and Free University of Berlin (FUB) have shown that dissociative electron attachment is a dominant process at low electron energies and is both bond (C-H versus C-N) and site selective (N1-H versus N3-H) in the DNA bases. These pioneering results suggest that may be possible to explore DNA damage at a basic molecular level. Indeed recent work by FUB, UIBK and Open University (OU) has demonstrated a correlation between electron attachment rates to biomolecules and their carcinogenicity and may be used to suggest new compounds to be adopted in radiation therapy as treatment enhancing sensitizers, e.g. 5-bromouracil. Complementary theoretical calculation (performed by La Sapienza University Rome) on the dynamics of Uracil fragmentation after electron attachment has likewise been published in PRL and received widespread publicity. These results provide significant consequences for the molecular description of genotoxic effects in living cells due to low-energy electrons, which are found to be the most abundant secondary species formed from ionizing radiation.

Through STSMs the Action has helped to develop a strong programme in the study of spectroscopy and dissociation dynamics of biomolecules under electron and photon impact. This work has been led by the OU, New University of Lisbon, Institute of Physics Belgrade, Comenius University Slovakia and University of Iceland. Studies on the effect of the local media on dissociation dynamics has led to several surface science type experiments being developed (e.g. by University of Paris-Sud and Free University Berlin (a fruitful collaboration funded by STSMs)

The use of photons and synchrotron radiation to explore biomolecular structure and DNA damage has also been pursued under the remit of WG1. Recent results by OU and University of Aarhus have provided new quantitative results of DNA damage as a function of UV dose, information that may be used in epidemological models.

Such pioneering research has led to an active and growing international research community, one in which the EU is recognised as amongst the most active and leading members.

WG2 In similar way to WG1 had developed a series of collaborative projects with Groningen, Queens University of Belfast and GNIL Caen cooperating on ion impact studies of nucleotide bases and, co-operating with HMI Berlin and ATOMKI Hungary, in the study of ion induced fragmentation of water. Indeed so much data was collected on water that this was the topic of its own workshop in 2006. The collaborative work in Groningen had also led to the exciting potential observation of Watson-Crick pair in clusters of the nucleotide bases. Several experiments are now in development to study biomolecules in clusters (Aarhua, Groeningen, Innsbruck and Lyons) as a method for exploring the role of local medium in radiation damage (e.g. in release of OH radical form water embedded in DNA). Once again the ability to co-ordinate such work through STSMs has proven to be invaluable allowing the groups to develop common experimental techniques.

WG3 had encouraged a wide variety of visits and collaborations in several areas of Radiation damage including free radical chemistry, protein damage and DNA damage studies as well as several in vivo experiments. The importance of bystander effect has been highlighted (Dublin Institute of Technology and Gray Caner Lab, UK) and in late 2006 a new research topic, the study of radiation damage on cellular membranes has emerged. This WG has also resulted in the most applied research with the Chair Dr K McGuigan technique for solar UV water sterilization being featured internationally as a cheap yet effective method for water treatment in poor countries and applicable in regions of Natural Disaster (e.g. tsunami).

WG4 has developed a strong programme to explore and develop computational methods for calculating the electronic states of biomolecules and studying biomolecular fragmentation patterns under different ionizing radiations. Much of the work undertaken in STSMs of WG4 involved a theoretical study of the interaction of ions with biomolecules and photochemistry and photodissociation processes. This work also allows interpretation of experimental results in WG1 and WG2. New advances in ab initio calculations of the potential energy hypersurfaces for the ground state, and especially for excited states have been made. The role played by the triplet excited states, and therefore by the intersystem interaction being demonstrated. The problem of the DNA base staking and its correct ab initio description has also been addressed. This problem is central to the understanding of for example electron migration or ionized stacks of bases in DNA. One of the essential issues when modelling the decay mechanism is the correct location of the important features on the energy landscapes such as minima, transition states or conical intersections. In this sense, nonadiabatic dynamics around conical intersections appears to be more a general mechanism of de-excitation for excited states than an exception. However, a correct choice of both the reaction paths and of the active coordinates defining the nuclear motions are necessary to describe the dynamical processes. The types of processes that were discussed were numerous. These included photodissociation, photoisomerization or intra and inter charge transfer mechanisms to the optimal control of selective photofragmentation to repair DNA mutation or even investigation of the production of multiply charged ions by core excitation of biomolecules. Finally, the inclusion of solvent effects has been investigated. It is important to note that the biological systems considered are not only the DNA and RNA bases or bases pairs and peptides but also chromophores of protein or of visual pigments.

WG5 has concentrated upon the development of radiation damage models which are of particular relevance to understanding the risk of exposure to different types of ionising radiation. The WG has identified the following key questions;

  • At which stages (initiation/promotion/clonal progression) does radiation contribute most to carcinogenesis and is this the same across tissues, radiation qualities, doses and dose rates?
  • Which of the three common mechanistic risk projection models is most soundly based upon biological evidence? Carcinogenesis driven by
    1. Direct targeted DNA damage in single cells
    2. Non-targeted damage in single cells
    3. Tissue level inflammatory responses
  • How can the contribution of inherited factors to individual risks be incorporated into mathematical risk projection models?
  • What is the mathematical model for cancer risk projection that is most consistent with available data and what are the operational consequences

STSMs have explored current models and their development and also identified the key fundamental data that is necessary for their improvement (tasks for the other WGS).