Can Monte Carlo track structure codes reveal reaction mechanism in DNA damage and improve radiation therapy?

Abstract

Microdosimetry and track structure have been applied to scrutinize and understand aspects of radiation damage in biological molecules from a theoretical approach based on fundamental physical and chemical principles to provide hypothesis which are testable experimentally. To this end, track structure has provided a basis for understanding the mechanism(s) that shape dose–effect relationships. There is a wealth of information and data accumulated from chemical, cellular and molecular radiation biology that need to be placed in the framework of a general descriptive theory. While there are many classical radiobiology questions remain unanswered, new ideas and challenging questions are emerging. Among many, simulation of radiation track at molecular level is an emerging tool in radiobiology and theoretical radiotherapy. How can we update track structure codes to include and test current reaction mechanism(s) in DNA damage? How realistic can we simulate radiation tracks in well-defined DNA model systems as well as DNA in a tissue environment? To what extent can we probe DNA damage induced by electron and ion tracks through the cell? Can we predict the frequency and complexity of biological lesions? How can models of track structure be improved to provide more accurate information for therapy and risk estimation? In this paper, we present recent progress in development of low-energy electron tracks in condensed media and high-energy proton tracks and discuss progress in characterizing DNA damage in terms of types and complexity.