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Title: Relative Biological Effectiveness of Energetic Heavy Ions for Intestinal Tumorigenesis Shows Male Preponderance and Radiation Type and Energy Dependence in APC{sup 1638N/+} Mice

Abstract

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 γ radiation. Methods and Materials: Male and female APC{sup 1638N/+} mice (n=20 mice per group) were whole-body exposed to sham-radiation, γ rays, {sup 12}C, {sup 28}Si, or {sup 56}Fe radiation. For the >1 Gy HZE dose, we used γ-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 tumors was observed after {sup 28}Si, followed by {sup 56}Fe and {sup 12}C radiation, and tumorigenesis showed a male preponderance, especially after {sup 28}Si. 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 value with {sup 28}Si, and lower dosesmore » 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/μm. Our study has implications for understanding risk to astronauts undertaking long duration space missions.« less

Authors:
; ; ; ; ;  [1];  [2];  [1];  [1]
  1. Department of Biochemistry and Molecular & Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia (United States)
  2. Department of Cell Biology, UT Southwestern Medical Center, Dallas, Texas (United States)
Publication Date:
OSTI Identifier:
22648623
Resource Type:
Journal Article
Journal Name:
International Journal of Radiation Oncology, Biology and Physics
Additional Journal Information:
Journal Volume: 95; Journal Issue: 1; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0360-3016
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; 62 RADIOLOGY AND NUCLEAR MEDICINE; CARBON 12; ENERGY DEPENDENCE; GAMMA RADIATION; GY RANGE 01-10; HEAVY IONS; IRON 56; KEV RANGE 10-100; LARGE INTESTINE; LET; MICE; NEOPLASMS; RADIATION HAZARDS; RADIOTHERAPY; RBE; SILICON 28

Citation Formats

Suman, Shubhankar, Kumar, Santosh, Moon, Bo-Hyun, Strawn, Steve J., Thakor, Hemang, Fan, Ziling, Shay, Jerry W., Fornace, Albert J., Center of Excellence in Genomic Medicine Research, and Datta, Kamal. Relative Biological Effectiveness of Energetic Heavy Ions for Intestinal Tumorigenesis Shows Male Preponderance and Radiation Type and Energy Dependence in APC{sup 1638N/+} Mice. United States: N. p., 2016. Web. doi:10.1016/J.IJROBP.2015.10.057.
Suman, Shubhankar, Kumar, Santosh, Moon, Bo-Hyun, Strawn, Steve J., Thakor, Hemang, Fan, Ziling, Shay, Jerry W., Fornace, Albert J., Center of Excellence in Genomic Medicine Research, & Datta, Kamal. Relative Biological Effectiveness of Energetic Heavy Ions for Intestinal Tumorigenesis Shows Male Preponderance and Radiation Type and Energy Dependence in APC{sup 1638N/+} Mice. United States. doi:10.1016/J.IJROBP.2015.10.057.
Suman, Shubhankar, Kumar, Santosh, Moon, Bo-Hyun, Strawn, Steve J., Thakor, Hemang, Fan, Ziling, Shay, Jerry W., Fornace, Albert J., Center of Excellence in Genomic Medicine Research, and Datta, Kamal. Sun . "Relative Biological Effectiveness of Energetic Heavy Ions for Intestinal Tumorigenesis Shows Male Preponderance and Radiation Type and Energy Dependence in APC{sup 1638N/+} Mice". United States. doi:10.1016/J.IJROBP.2015.10.057.
@article{osti_22648623,
title = {Relative Biological Effectiveness of Energetic Heavy Ions for Intestinal Tumorigenesis Shows Male Preponderance and Radiation Type and Energy Dependence in APC{sup 1638N/+} Mice},
author = {Suman, Shubhankar and Kumar, Santosh and Moon, Bo-Hyun and Strawn, Steve J. and Thakor, Hemang and Fan, Ziling and Shay, Jerry W. and Fornace, Albert J. and Center of Excellence in Genomic Medicine Research and Datta, Kamal},
abstractNote = {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 γ radiation. Methods and Materials: Male and female APC{sup 1638N/+} mice (n=20 mice per group) were whole-body exposed to sham-radiation, γ rays, {sup 12}C, {sup 28}Si, or {sup 56}Fe radiation. For the >1 Gy HZE dose, we used γ-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 tumors was observed after {sup 28}Si, followed by {sup 56}Fe and {sup 12}C radiation, and tumorigenesis showed a male preponderance, especially after {sup 28}Si. 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 value with {sup 28}Si, 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/μm. Our study has implications for understanding risk to astronauts undertaking long duration space missions.},
doi = {10.1016/J.IJROBP.2015.10.057},
journal = {International Journal of Radiation Oncology, Biology and Physics},
issn = {0360-3016},
number = 1,
volume = 95,
place = {United States},
year = {2016},
month = {5}
}