A Model of Cell Damage in Space Flight

Abstract

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 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. Biological Effects and Physics of Solar and Galactic Cosmic