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

The effect of all types of ionizing radiations on higher organisms is nonsp ecific in the sense that all interactions occur through the agency of ioniz ation and excitation processes. This, and the relative constancy of the amo unt of energy required to induce such processes, has led to the concept of absorbed dose as a quantifier for the amount of radiation delivered. Howeve r, 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 t hese factors, it follows that the biological effectiveness of ionizing radi ation depends on their spatial and temporal configuration. Microdosimetry i s the study of the distribution in space and time of elementary energy depo sits and their relation to subsequent damage. We discuss physico-chemical e vents that occur within the first microsecond following the interaction of charged particles with deoxyribonucleic acid (DNA) and argue that this part icular time interval is uniquely important for understanding the biological effectiveness of radiation. Radiation biologists distinguish between direc t hits and damage induced-indirectly by radicals produced in the condensed medium surrounding the DNA target. The interaction and diffusion of these r adicals (primarily OH) are described with the techniques of stochastic chem istry because - unlike "regular" chemistry - their initial spatial distribu tion is highly nonuniform. The information thus obtained is usually summari zed in terms of proximity functions or microdosimetric distributions. The u ltimate object of such studies is to obtain information on specific DNA alt erations (e.g., strand breaks) or chromosomal damage and correlate them to such events as mutagenesis and carcinogenesis. (C) 2000 John Wiley & Sons, Inc.