Molecular mechanism underlying heavy ion therapy

The current increasing social and corporate interest in proton- and heavy ion-therapy of malignant tumours lead to an increasing number of treatment facilities worldwide. When fast ions traverse tissue and are decelerated to MeV energies and below, the so-called Bragg-peak is reached. At this well-defined depth, damage is highest due to maximum linear energy transfer and radiobiological effectiveness at these energies. This volume sensitivity renders ion-therapy a superior tool for a number of tumors, often decreasing the yearly risk of radiation induced development of lethal secondary tumors by up to one order of magnitude! The chemical and biological aspects of biological radiation damage have been studied in great detail. Whereas for conventional radiation the molecular mechanisms underlying biological action are to some extent understood, the exceptional cell killing efficiency of heavy ions and protons is largely unexplored on the molecular level. In Groningen we recently observed fragment ion kinetic energies exceeding 10 eV when irradiating isolated DNA building blocks with ions at Bragg-peak energies. Such energetic fragments can in turn induce further ionization and fragmentation of DNA building blocks, leading to an avalanche of damage that could manifest in clustered DNA lesions. Currently, more complex targets such as electrosprayed nanosolvated biomolecules and biomolecular complexes are employed to extend radiation damage studies to more realistic systems. First results indicate that a chemical environment opens up additional fragmentation channels for DNA building blocks. Water solvation shells, on the other hand, seem to prevent fragmentation.