Chromosome aberrations induced by GCR-simulated mixed-beam exposure in human and mouse cells - Computational model prediction and biological validation

The NASA Space Radiation Laboratory (NSRL) has been upgraded to rapidly switch ions and energies to allow investigators to design irradiation protocols comprising a mixture of ions and energies more indicative of the galactic cosmic ray (GCR) environment. Beam selection and delivery schemes were optimized against facility and experimental constraints, and need to be validated to ensure such irradiations are a suitable representation of the space environment. Importantly, since experiments are time consuming and expensive, models capable of predicting biological outcomes over a range of irradiation conditions (single ion, sequential multi-ion, or mixed fields) are needed to confirm our understanding, and to support estimates of risk for untested complex space radiation environments. We investigated chromosome aberrations (CA) induced in human blood lymphocytes, skin fibroblast, epithelial cells and bone marrow lymphocytes from female mice (CB6F1 mice of 100-120 days of age) that were exposed to single and mixed beams (2-ions, 3-ions, 4-ions or 6-ions mix) of Proton, Helium, Oxygen, Silicon, Titanium, and Iron-ions at NSRL. Chromosomes from human cells were collected with the premature chromosome condensation method in the first mitosis. Chromosomes from mouse bone marrow were collected 16 months after exposure. CA yield was measured with 3-color fluorescent in situ hybridization (FISH) chromosome painting. A combination of models and programs were used to simulate CA in fibroblast cells. The code Geant4 was used to calculate the distribution of particles behind shielding after irradiation. Using calculated particle spectra, the code RITRACKS (Relativistic Ion Track) generated time-dependent differential 3D voxel dose maps, which were used in RITCARD (Radiation Induced Tracks, Chromosome Aberrations, Repair and Damage) to simulate CA in human fibroblasts. The multi-scale model described here is a major milestone toward developing computational tools to predict biological outcomes in a complex ion field environment. The simulation and experimental results are in good agreement, suggesting that the model may be highly useful in further design of a ground-based GCR simulator and for informing risk projection models in the future. Mixed beam data of human fibroblast CA were also analyzed using Incremental Effect Additivity (IEA) synergy theory, rather than the Simple Effect Additivity (SEA) synergy theory that has long been discredited for dealing with highly curvilinear Dose-Effect Relationship (DER). Results from the synergy modeling suggest neither synergy nor antagonism (NSNA). Supported by NASA Grants # NNJ16HP22I, NNX16AR97G and TAMU-CRI.