Investigation into the foundations of the track-event theory of cell survival and the radiation action model based on nanodosimetry.

This work aims at elaborating the basic assumptions behind the "track-event theory" (TET) and its derivate "radiation action model based on nanodosimetry" (RAMN) by clearly distinguishing between effects of tracks at the cellular level and the induction of lesions in subcellular targets. It is demonstrated that the model assumptions of Poisson distribution and statistical independence of the frequency of single and clustered DNA lesions are dispensable for multi-event distributions because they follow from the Poisson distribution of the number of tracks affecting the considered target volume. It is also shown that making these assumptions for the single-event distributions of the number of lethal and sublethal lesions within a cell would lead to an essentially exponential dose dependence of survival for practically relevant values of the absorbed dose. Furthermore, it is elucidated that the model equation used for consideration of repair within the TET is based on the assumption that DNA lesions induced by different tracks are repaired independently. Consequently, the model equation is presumably inconsistent with the model assumptions and requires an additional model parameter. Furthermore, the methodology for deriving model parameters from nanodosimetric properties of particle track structure is critically assessed. Based on data from proton track simulations it is shown that the assumption of statistically independent targets leads to the prediction of negligible frequency of clustered DNA damage. An approach is outlined how track structure could be considered in determining the model parameters, and the implications for TET and RAMN are discussed.

CONSIDERATIONS ON THE TARGET SIZE IN A WALL-LESS NANODOSIMETER.

In nanodosimetry, the ionization component of charged particle track structure is characterized by measuring the frequency distribution of ionizations in target volumes that simulate nanometric sites in liquid water. For the Ion Counter nanodosimeter at PTB, the sensitive volume is defined by the electrical field and the extraction aperture. In this paper, a procedure is presented to define a cylindrical effective measurement target based on the second moments of the detection efficiency map. An analytical model of the efficiency map is developed to investigate the dependence of the simulated site size on the nanodosimeter's operating parameters. Within the limits of the simplifying assumptions, the model gives a reasonable approximation of the efficiency map.