A Model of Cell Damage in Space Flight

Cell damage by high LET radiations has been described by a phenomenological model (track theory) for 20 years and more. Molecules of biological significance (dry enzymes and viruses) act as 1 hit detectors. Recent additions to the class of I-hit detectors are E. Coli B, and the creation of both single and double strand breaks in SV-40 virus in EO buffer, where indirect effects predominate. The response of cells (survival, transformation, chromosome aberration) to these radiations is typically described by a 4-parameter model whose numerical values are determined by fitting the equations of the theory to experimental data at high dose (typically above 1 Gy) with bombardments with 'Y rays and HZE particle beams, of the widest possible dynamic range. Once these parameters are determined the model predicts cellular response in any radiation environment whose particle-energy spectrum is !mown. Perhaps the central importance of the present model is the ability to estimate the response of a complex environment with many components from a limited set of laboratory data. For example, we have calculated cell survival after neutron irradiation, with mixtures of neutrons and 'Y rays; cell survival and transformation after irradiation with HZE ions of different energies. The model does not yet include cellular repair. Although some hopeful approaches to repair dependence are now being developed. It does not include cancer induction, for the available data neither give the number of cells at risk or the number of cancers induced, and are thus not suited to our formulation. Most recently NASA-Langley models of HZE beams, including projectile and target fragmentation, have been joined with the biological model. This combination has been tested against ground based radiobiological data for cell survival after irradiation with protons and HZE beams with good success. Where our earlier model failed downstream of the Bragg Biological Effects and Physics of Solar and Galactic Cosmic Radiation, Part A. Edited by C.E. Swenberg et al.• Plenum Press. New York, 1993 235 peak (for both protons and heavy ions) for want of a proper description of fragmentation the NASA-Langley model succeeds. Based on this experimental validation of our procedures, we have initiated calculations of cellular damage in space flight from solar protons and galactic cosmic rays. Here we incorporate NASA models of cosmic rays, beam penetration, projectile and target fragmentation with track theory. The essential radiobiological theme is that knowledge of parameters extracted at high doses makes it possible for us to calculate the response of cells at the lowest possible doses of HZE particles when only intra track (ion-kill) effects are involved for which repair is known to be minimal. Our procedures here too have ground based experimental validation in recent work of Bettega et al. where measurements made of RBE with protons and alphas of the survival of C3HlOTl/2 cells, at doses down to 0.01 Gy are consistent with our predictions based on survival measurements made at high doses with 'Y rays and HZE ions. INTRODUCTION Detectors of radiation differ according to whether single particle response is normally observed, as with nuclear emulsions, solid state nuclear track detectors, and scintillation counters, or whether the response is to beams of particles or photons in a gross macroscopic irradiation, as in radiobiology or in the alteration of bulk material properties by radiation. In the former case it is more natural to think in terms of track structure, while in the latter case one frequently refers to macroscopic dose (Katz, 1978). Response is then correlated to the physical description of these stimula. It is common to relate response to energy deposition (dose). Problems arise because response depends not only on total energy deposition but on the microscopic structure of that deposition and also on its time development. One analysis of these details is called microdosimetry, a subject that has stimulated many investigations. An alternate procedure favored here relates the observed effect to track structure for individual particles, which then may be related to macroscopic dose for gross irradiations. These perspectives are principally reported in the several Symposia on Microdosimetry sponsored by the Commission of European Communities. The galactic cosmic ray (GCR) environment is the most complicated mixture of radiation components known. It is doubtful that the GCR will ever be adequately simulated in the laboratory for biological experiments. The primary role of track structure models will be to extrapolate laboratory response data to the GCR environment for the estimate of risk to biological tissues in space exposure. This is, we believe, to be a more practical approach to the issue of additivity of response of disparate components than the usual quality factor approach based on relative biological effectiveness (RBE) which has been used with limited success in terrestrial radiation protection. We will now discuss the current approaches to the question of additivity being pursued by various groups. ENERGY DEPOSITION IN SMALL VOLUMES: MICRODOSIMETRY One way to analyze the stimulus to biological systems is to examine the details of energy deposition in small volumes, sized to represent what are thought to be critical targets within the cell. Experimentally small gaseous proportional counters are used whose diameter, scaled to the density of tissue, is from micrometers to nanometers in unit density material. The critical targets are then considered to be either the nucleus of a mammalian cell or a chromosome, or a small region of DNA. The fluctuations of the energy deposited within the small target region is assumed related to biological response. A Monte Carlo simulation of a radiation field can yield a similar decomposition. Even when one has a complete microdosimetric description of the radiation environment, the problem remains as to how that may be interpreted to predict the response of a detector. As yet we have no means of calibrating response in terms of the statistical distribution of energy depositions in small volumes. Nor do we know what volume is appropriate. It is on this level that microdosimetry has not been able to make extensive quantitative predictions,