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Title: Harderian Gland Tumorigenesis: Low-Dose and LET Response

Abstract

Increased cancer risk remains a primary concern for travel into deep space and may preclude manned missions to Mars due to large uncertainties that currently exist in estimating cancer risk from the spectrum of radiations found in space with the very limited available human epidemiological radiation-induced cancer data. Existing data on human risk of cancer from X-ray and gamma-ray exposure must be scaled to the many types and fluences of radiations found in space using radiation quality factors and dose-rate modification factors, and assuming linearity of response since the shapes of the dose responses at low doses below 100 mSv are unknown. The goal of this work was to reduce uncertainties in the relative biological effect (RBE) and linear energy transfer (LET) relationship for space-relevant doses of charged-particle radiation-induced carcinogenesis. The historical data from the studies of Fry et al. and Alpen et al. for Harderian gland (HG) tumors in the female CB6F1 strain of mouse represent the most complete set of experimental observations, including dose dependence, available on a specific radiation-induced tumor in an experimental animal using heavy ion beams that are found in the cosmic radiation spectrum. However, these data lack complete information on low-dose responses below 0.1more » Gy, and for chronic low-dose-rate exposures, and there are gaps in the LET region between 25 and 190 keV/μm. In this study, we used the historical HG tumorigenesis data as reference, and obtained HG tumor data for 260 MeV/u silicon (LET ~70 keV/μm) and 1,000 MeV/u titanium (LET ~100 keV/μm) to fill existing gaps of data in this LET range to improve our understanding of the dose-response curve at low doses, to test for deviations from linearity and to provide RBE estimates. Animals were also exposed to five daily fractions of 0.026 or 0.052 Gy of 1,000 MeV/u titanium ions to simulate chronic exposure, and HG tumorigenesis from this fractionated study were compared to the results from single 0.13 or 0.26 Gy acute titanium exposures. Theoretical modeling of the data show that a nontargeted effect model provides a better fit than the targeted effect model, providing important information at space-relevant doses of heavy ions.« less

Authors:
 [1];  [2];  [3];  [4];  [4];  [3];  [3];  [2];  [3]
  1. SRI International, Menlo Park, CA (United States). Biosciences Div.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.
  2. Univ. of Nevada, Las Vegas, NV (United States). Dept. of Health Physics and Diagnostic Sciences
  3. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.
  4. SRI International, Menlo Park, CA (United States). Biosciences Div.
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
OSTI Identifier:
1378356
DOE Contract Number:  
AC02-05CH11231
Resource Type:
Journal Article
Journal Name:
Radiation Research
Additional Journal Information:
Journal Volume: 185; Journal Issue: 5; Journal ID: ISSN 0033-7587
Publisher:
Radiation Research Society
Country of Publication:
United States
Language:
English
Subject:
38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY; 63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.

Citation Formats

Chang, Polly Y., Cucinotta, Francis A., Bjornstad, Kathleen A., Bakke, James, Rosen, Chris J., Du, Nicholas, Fairchild, David G., Cacao, Eliedonna, and Blakely, Eleanor A. Harderian Gland Tumorigenesis: Low-Dose and LET Response. United States: N. p., 2016. Web. doi:10.1667/RR14335.1.
Chang, Polly Y., Cucinotta, Francis A., Bjornstad, Kathleen A., Bakke, James, Rosen, Chris J., Du, Nicholas, Fairchild, David G., Cacao, Eliedonna, & Blakely, Eleanor A. Harderian Gland Tumorigenesis: Low-Dose and LET Response. United States. doi:10.1667/RR14335.1.
Chang, Polly Y., Cucinotta, Francis A., Bjornstad, Kathleen A., Bakke, James, Rosen, Chris J., Du, Nicholas, Fairchild, David G., Cacao, Eliedonna, and Blakely, Eleanor A. Tue . "Harderian Gland Tumorigenesis: Low-Dose and LET Response". United States. doi:10.1667/RR14335.1.
@article{osti_1378356,
title = {Harderian Gland Tumorigenesis: Low-Dose and LET Response},
author = {Chang, Polly Y. and Cucinotta, Francis A. and Bjornstad, Kathleen A. and Bakke, James and Rosen, Chris J. and Du, Nicholas and Fairchild, David G. and Cacao, Eliedonna and Blakely, Eleanor A.},
abstractNote = {Increased cancer risk remains a primary concern for travel into deep space and may preclude manned missions to Mars due to large uncertainties that currently exist in estimating cancer risk from the spectrum of radiations found in space with the very limited available human epidemiological radiation-induced cancer data. Existing data on human risk of cancer from X-ray and gamma-ray exposure must be scaled to the many types and fluences of radiations found in space using radiation quality factors and dose-rate modification factors, and assuming linearity of response since the shapes of the dose responses at low doses below 100 mSv are unknown. The goal of this work was to reduce uncertainties in the relative biological effect (RBE) and linear energy transfer (LET) relationship for space-relevant doses of charged-particle radiation-induced carcinogenesis. The historical data from the studies of Fry et al. and Alpen et al. for Harderian gland (HG) tumors in the female CB6F1 strain of mouse represent the most complete set of experimental observations, including dose dependence, available on a specific radiation-induced tumor in an experimental animal using heavy ion beams that are found in the cosmic radiation spectrum. However, these data lack complete information on low-dose responses below 0.1 Gy, and for chronic low-dose-rate exposures, and there are gaps in the LET region between 25 and 190 keV/μm. In this study, we used the historical HG tumorigenesis data as reference, and obtained HG tumor data for 260 MeV/u silicon (LET ~70 keV/μm) and 1,000 MeV/u titanium (LET ~100 keV/μm) to fill existing gaps of data in this LET range to improve our understanding of the dose-response curve at low doses, to test for deviations from linearity and to provide RBE estimates. Animals were also exposed to five daily fractions of 0.026 or 0.052 Gy of 1,000 MeV/u titanium ions to simulate chronic exposure, and HG tumorigenesis from this fractionated study were compared to the results from single 0.13 or 0.26 Gy acute titanium exposures. Theoretical modeling of the data show that a nontargeted effect model provides a better fit than the targeted effect model, providing important information at space-relevant doses of heavy ions.},
doi = {10.1667/RR14335.1},
journal = {Radiation Research},
issn = {0033-7587},
number = 5,
volume = 185,
place = {United States},
year = {2016},
month = {4}
}