Abstract
The biological effects of high charge and energy (HZE) particle exposures are of interest in space radiation protection of astronauts and cosmonauts, and estimating secondary cancer risks for patients undergoing Hadron therapy for primary cancers. The large number of particles types and energies that makeup primary or secondary radiation in HZE particle exposures precludes tumor induction studies in animal models for all but a few particle types and energies, thus leading to the use of surrogate endpoints to investigate the details of the radiation quality dependence of relative biological effectiveness (RBE) factors. In this report we make detailed RBE predictions of the charge number and energy dependence of RBE’s using a parametric track structure model to represent experimental results for the low dose response for chromosomal exchanges in normal human lymphocyte and fibroblast cells with comparison to published data for neoplastic transformation and gene mutation. RBE’s are evaluated against acute doses of γ-rays for doses near 1 Gy. Models that assume linear or non-targeted effects at low dose are considered. Modest values of RBE (<10) are found for simple exchanges using a linear dose response model, however in the non-targeted effects model for fibroblast cells large RBE values (>10) are predicted at low doses <0.1 Gy. The radiation quality dependence of RBE’s against the effects of acute doses γ-rays found for neoplastic transformation and gene mutation studies are similar to those found for simple exchanges if a linear response is assumed at low HZE particle doses. Comparisons of the resulting model parameters to those used in the NASA radiation quality factor function are discussed.
Highlights
Estimating high LET radiation carcinogenesis risk is of interest in studies of normal tissue damage in Hadron cancer therapy with protons, carbon and other heavy ion beams, and space radiation protection during space travel
Prior results did not reveal a significant difference in the linear slopes for exchanges for the small number of volunteers used in these experiments [18,19,26]
In this report we focused on the radiation quality dependence of relative biological effectiveness (RBE)’s for surrogate endpoints of cancer risk in cell culture models, and how RBE values are influenced by possible non-targeted effect (NTE)
Summary
Estimating high LET radiation carcinogenesis risk is of interest in studies of normal tissue damage in Hadron cancer therapy with protons, carbon and other heavy ion beams, and space radiation protection during space travel. Relative Biological Effectiveness of HZE Particles adherence to PLOS ONE policies on sharing data and material. Major challenges for high LET risk estimation are the absence of human epidemiology data, and the quantitative and qualitative differences in their biological effects compared to low LET radiation found in experimental studies with murine or cell culture models [1,2]. In Hadron therapy with carbon beams an RBE for cell killing is applied such that the dose per fraction of less than 1 Gy often occurs, while a large range of total doses overall fractions (0 to >10 Gy) occur in normal tissues away from tumor sites [6,7]. Mechanisms of biological damage are likely distinct at high dose compared to low dose, and the smaller signal at low dose is a major obstacle for animal experiments to be performed with statistically significant sample sizes
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