From track structure to stochastic chemistry and DNA damage: Microdosimetric perspective

The effect of all types of ionizing radiations on higher organisms is nonspecific in the sense that all interactions occur through the agency of ionization and excitation processes. This, and the relative constancy of the amount of energy required to induce such processes, has led to the concept of absorbed dose as a quantifier for the amount of radiation delivered. However, equal doses of different radiations have different effects depending on the stopping power of the charged particles and on the temporal pattern of irradiation. Because individual energy transfers depend on neither one of these factors, it follows that the biological effectiveness of ionizing radiation depends on their spatial and temporal configuration. Microdosimetry is the study of the distribution in space and time of elementary energy deposits and their relation to subsequent damage. We discuss physico‐chemical events that occur within the first microsecond following the interaction of charged particles with deoxyribonucleic acid (DNA) and argue that this particular time interval is uniquely important for understanding the biological effectiveness of radiation. Radiation biologists distinguish between direct hits and damage induced indirectly by radicals produced in the condensed medium surrounding the DNA target. The interaction and diffusion of these radicals (primarily OH) are described with the techniques of stochastic chemistry because—unlike “regular” chemistry—their initial spatial distribution is highly nonuniform. The information thus obtained is usually summarized in terms of proximity functions or microdosimetric distributions. The ultimate object of such studies is to obtain information on specific DNA alterations (e.g., strand breaks) or chromosomal damage and correlate them to such events as mutagenesis and carcinogenesis. © 2000 John Wiley & Sons, Inc. Int J Quant Chem 80: 327–340, 2000