Relative Biological Effectiveness of Energetic Heavy Ions for Intestinal Tumorigenesis Shows Male Preponderance and Radiation Type and Energy Dependence in APC1638N/+ Mice

Purpose: There are uncertainties associated with the prediction of colorectal cancer (CRC) risk from highly energetic heavy ion (HZE) radiation. We undertook a comprehensive assessment of intestinal and colonic tumorigenesis induced after exposure to high linear energy transfer (high-LET) HZE radiation spanning a range of doses and LET in a CRC mouse model and compared the results with the effects of low-LET gamma radiation. Methods and Materials: Male and female APC(1638N/+) mice (n=20 mice per group) were whole-body exposed to sham-radiation, gamma rays, C-12, Si-28, or Fe-56 radiation. For the > 1 Gy HZE dose, we used gamma-ray equitoxic doses calculated using relative biological effectiveness (RBE) determined previously. The mice were euthanized 150 days after irradiation, and intestinal and colon tumor frequency was scored. Results: The highest number of tumorswas observed after Si-28, followed by Fe-56 and C-12 radiation, and tumorigenesis showed a male preponderance, especially after Si-28. Analysis showed greater tumorigenesis per unit of radiation (per cGy) at lower doses, suggesting either radiation-induced elimination of target cells or tumorigenesis reaching a saturation point at higher doses. Calculation of RBE for intestinal and colon tumorigenesis showed the highest valuewith Si-28, and lower doses showed greater RBE relative to higher doses. Conclusions: We have demonstrated that the RBE of heavy ion radiation-induced intestinal and colon tumorigenesis is related to ion energy, LET, gender, and peak RBE is observed at an LET of 69 keV/mm. Our study has implications for understanding risk to astronauts undertaking long duration space missions. (C) 2016 Elsevier Inc. All rights reserved.